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This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Adhesive Capsulitis of the Shoulder patients must be diagnosed as having idiopathic adhesive capsulitis in the 'frozen' or 'thawing' phase of disease and have tried and failed at least 3 months of nonoperative therapy. OR patient with adhesive capsulitis who presents already in the 'frozen' or 'thawing' phase who demands a quicker return to function and will not try 3 months of nonoperative therapy first Age 18 or older pregnancy previously operated shoulder (same side) other documented source of shoulder pain and stiffness (same side) rotator cuff tear (same side) glenohumeral osteoarthritis (same side) calcific tendonitis (same side) impingement (same side) osteonecrosis neoplasm cervical radiculopathy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Eastern Cooperative Oncology Group performance status of 0-1 Diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that meets protocol-defined Laboratory values within protocol-defined parameters Active disease meeting International Workshop on Chronic Lymphocytic Leukemia 2008 Received at least 1 prior therapy for CLL/SLL and not appropriate for treatment or retreatment with purine analog-based therapy Measurable nodal disease by computed tomography Female subjects of childbearing potential must have a negative serum or urine pregnancy test at Screening and agree to use highly effective methods of contraception during the study and for 90 days following the last dose with ibrutinib or 12 months following the last dose of rituximab Central nervous system lymphoma or leukemia Prolymphocytic leukemia or history of or currently suspected Richter's transformation Refractory to prior rituximab-based therapy Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days prior to first dose of study drug Corticosteroid use >20 mg within 1 week prior to first dose of study drug Radio or toxin-conjugated antibody therapy within 10 weeks prior to first dose of study drug Prior autologous transplant within 6 months prior to first dose of study drug Prior allogeneic stem cell transplant Major surgery within 4 weeks prior to first dose of study drug | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Key Documented diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) No prior therapy for CLL other than corticosteroids for disease complications CLL that warrants treatment Presence of measurable lymphadenopathy Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Key Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation) Known presence of myelodysplastic syndrome Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization Ongoing liver injury History of non-infectious pneumonitis Ongoing inflammatory bowel disease History of prior allogeneic bone marrow progenitor cell or solid organ transplantation Ongoing immunosuppressive therapy other than corticosteroids Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization Note: Other protocol defined Inclusion/ | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 40.0-65.0, Adult Lymphoblastic Lymphoma Disease ALL in complete remission (CR) at the time of transplant. Remission is defined as "less than 5.0% bone marrow lymphoblasts by morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration Philadelphia chromosome positive ALL is allowed Lymphoid blastic crisis of CML will be included (provided that patients achieve CR) Age Equal or above age 40 and up to 65 years. If younger than 40, there must be comorbidities which preclude the patient to undergo CyTBI conditioning regimen Organ Function All organ function testing should be done within 28 days of study registration Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula: CrCl = (140-age) x weight (kg) x 0.85 (if female)/72 x serum creatinine (mg/dL) Hepatic Non-compliant to medications No appropriate caregivers identified HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive Active life-threatening cancer requiring treatment other than ALL Uncontrolled medical or psychiatric disorders Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration Active central nervous system (CNS) leukemia Preceding allogeneic HSCT Receiving intensive chemotherapy within 21 days of registration. Maintenance type of chemotherapy will be allowed | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Breast Cancer Nos Metastatic Recurrent Women Aged 18 years and over With an invasive breast cancer diagnosed by cytology or histology Tumors cT0 to cT3, CN0-3 No clinical evidence of metastasis at the time of Untreated including scored for breast cancer surgery in progress Patient receiving a social security system Patient mastering the French language Free and informed consent for additional biological samples, different questionnaires and collecting information on resource usage Metastatic breast cancer Local recurrence of breast cancer History of cancer within 5 years prior to entry into the trial other than basal cell skin or carcinoma in situ of the cervix Already received treatment for breast cancer ongoing Blood transfusion performed for less than six months Persons deprived of liberty or under supervision (including guardianship) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Thyroid Cancer Newly diagnosed with a first occurrence of thyroid cancer <2-4 weeks of diagnosis (i.e., histologically confirmed thyroid cancer (papillary, follicular, or medullary type; TNM classification system) Willing to participate in the EG meetings >18 years Alert and capable of giving free and informed consent Able to speak and read English or French Anaplastic thyroid cancer Karnofsky Performance Status (KPS) score <60 (rated by the Research Coordinator (RC) or referring physician) or expected survival <6 months according to clinical judgment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-65.0, Chronic Pain Women Clinical diagnosis of chronic pelvic pain More than eighteen years Non-menstrual or noncyclic pelvic pain Duration of pain of at least 6 months Duration of pain less than 6 months Women who were pregnant in the last 12 months | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Coronary Artery Stenosis Age ≥ 18 years Patient with an indication for PCI including angina (stable or unstable), silent ischemia (in absence of symptoms a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or FFR ≤0.80 must be present), or recent STEMI. For STEMI the time of presentation to the first treating hospital, whether a transfer facility or the study hospital, must be >24 hours prior to randomization and enzyme levels (CK-MB or Troponin) demonstrating that either or both enzyme levels have peaked Non-target vessel PCI are allowed prior to randomization depending on the time interval and conditions as follows: a. During Baseline Procedure: i. PCI of non-target vessels performed during the baseline procedure itself immediately prior to randomization if successful and uncomplicated defined as: <50% visually estimated residual diameter stenosis, TIMI Grade 3 flow, no dissection ≥ NHLBI type C, no perforation, no persistent ST segment changes, no prolonged chest pain, no TIMI major or BARC type 3 bleeding. b. Less than 24 hours prior to Baseline Procedure: i. Not allowed (see #3). c. 24 hours-30 days prior to Baseline Procedure: i. PCI of non-target vessels 24 hours to 30 days prior to randomization if successful and uncomplicated as defined above. ii. In addition, in cases where non-target lesion PCI has occurred 24-72 hours prior to the baseline procedure, at least 2 sets of cardiac biomarkers must be drawn at least 6 and 12 hours after the non-target vessel PCI. If cardiac biomarkers are initially elevated above the local laboratory upper limit of normal, serial measurements must demonstrate that the biomarkers are falling. d. Over 30 days prior to Baseline Procedure: iii. PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule. Angiographic (visual estimate) Treatment of up to three de novo target lesions, maximum of one de novo target lesion per vessel Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.25 mm and diameter stenosis ≥50% to <100% Lesion must be ≤28 mm long and can be covered by a single study stent with maximum length of 33 mm (note: multiple focal stenoses may be considered as a single lesion and be enrolled if they can be completely covered with one stent) TIMI flow 2 or 3 If more than one target lesion will be treated, the RVD and lesion length of each must meet the above criteria Planned procedures after the baseline procedure in either the target or non-target vessels STEMI within 24 hours of initial time of presentation to the first treating hospital, whether at a transfer facility or the study hospital or in whom enzyme levels (either CK-MB or Troponin)have not peaked PCI within the 24 hours preceding the baseline procedure and randomization Non-target lesion PCI in the target vessel within 12 months of the baseline procedure History of stent thrombosis Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP Known LVEF <30% Subject is intubated Relative or absolute contraindication to DAPT for 12 months (including planned surgeries that cannot be delayed, or subject is indicated for chronic oral anticoagulant treatment) Hemoglobin <10 g/dL | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymphocytic Leukemia, Chronic Adults >/=18 years Documented Cluster of Differentiation Antigen 20 (CD20) + B-Cell Chronic Lymphocytic Lymphoma (B-CLL) Previously untreated Chronic Lymphocytic Leukemia (CLL) requiring treatment according to the National Cancer Institute (NCI) Total Cumulative Illness Rating Scale (CIRS) > 6 and/or creatinine clearance < 70 ml/min Prior CLL therapy Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation) History of other malignancy unless the malignancy has been in remission without treatment for >/=2 years prior to enrolment, and except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, surgically treated low-grade prostate cancer, or ductal carcinoma in situ (DCIS) of the breast treated with lymphectomy alone Positive hepatitis serology (HBV, HCV) or positive HIV or Human T Cell Leukemia Virus (HTLV) testing Patients with active infection requiring systemic treatment | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Refractory Ascites Hepatic Hydrothorax Hepatic Encephalopathy Cirrhosis Cirrhosis (any etiology) Refractory ascites or hepatic hydrothorax and plan for TIPS placement Well-documented overt hepatic encephalopathy, either persistent or at the time of screening Any contraindication for TIPS placement Except for coagulopathy and thrombocytopenia (decided on an individual basis) Uncontrolled depression/anxiety disorder or use of antipsychotic drugs Active use of alcohol or illicit drugs History of dementia TIPS planned for another indication Active alcoholic liver disease | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-130.0, Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Richter's Syndrome Prolymphocytic Leukemia Men and women ≥ 18 years of age with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, ≥ 2 previous treatments for CLL/SLL. 2. Must have measurable CLL/SLL defined as ≥ 1 lymph node ≥ 2 cm as measured in the longest diameter. 3. Active disease meeting ≥ 1 of the following IWCLL 2008 for requiring treatment: 1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL). 2. Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly. 3. Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy. 4. Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 X 109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded. 5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy. 6. Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs: i. Unintentional weight loss ≥ 10% within the previous 6 months before Screening. ii. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection. iii. Night sweats for > 1 month before Screening without evidence of infection. 4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 5. Agreement to use highly effective methods of contraception during the study and for 2 days after the last dose of study drug if sexually active and able to bear or beget children (see Section 3.7.9 for list of highly effective methods of contraception). 6. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. 7. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations). 8. Removed at Amendment 11. for Treatment Subgroups 1. Treatment Naive only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL, who require treatment per National Cancer Institute (NCI) or International Working Group guidelines and a) do not want to receive chemoimmunotherapy or b) have comorbidities that would preclude chemoimmunotherapy. 2. Ibrutinib Intolerant only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL who are not tolerating ibrutinib due to ibrutinib-related AEs. 3. Richter's Syndrome/Prolymphocytic Leukemia Transformation only: Men and women ≥ 18 years of age and biopsy proven diffuse large B cell lymphoma (DLBCL) Richter's transformation or prolymphocytic leukemia transformation. 4. Ibrutinib R/R only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL whose best response after 2 cycles of ibrutinib therapy was SD or nonresponse or who initially responded to ibrutinib therapy and now have signs of clinical progression Prior malignancy, except for adequately treated basal cell, squamous cell skin cancer or in situ cervical cancer. Subjects with other prior malignancies from which the subject has been disease free for ≥ 2 years may be included if approved by the medical monitor. 2. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk. 3. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) ≤ 40%. 4. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass. 5. Any immunotherapy within 4 weeks of first dose of study drug. 6. For subjects with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s). 7. Relapsed after, or refractory to, prior BTK inhibitor therapy (Note: Does not apply to Ibrutinib R/R or Richter's Syndrome Group). 8. Any history of Richter's transformation (Note: Does not apply to Richter's Syndrome Group). 10. Central nervous system (CNS) involvement by lymphoma. 11. Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation. 12. Known history of human immunodeficiency virus (HIV) or serologic status indicating active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection or any uncontrolled active systemic infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded. 13. Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent). 14. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug. 15. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). 16. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug. 17. Major surgery within 4 weeks before first dose of study drug. 18. ANC < 0.75 x 109/L or platelet count < 50 x 109/L unless there is bone marrow involvement. 19. Total bilirubin > 1.5 x ULN (total bilirubin ≤ 2.5 x ULN allowed in subjects with autoimmune hemolytic anemia that is otherwise controlled); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN unless disease related. 20. Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN. 21. Significant screening ECG abnormalities including, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, or QTc ≥ 480 ms. 22. Cardiac troponin I levels above the limit of normal as specified by the manufacturer. 23. Breast feeding or pregnant. 24. History of bleeding diathesis (e.g., hemophilia, von Willebrand disease). 25. Concurrent participation in another therapeutic clinical trial. 26. Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female]. 27. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Anemia Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on Chronic Lymphocytic Leukemia (IWCLL) or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria; this includes previous documentation of Biopsy-proven small lymphocytic lymphoma or Diagnosis of CLL according to the NCI/IWCLL as evidenced by all of the following Peripheral blood lymphocyte count of greater than 5 x 10^9/L Immunophenotype consistent with CLL defined as The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc) Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression) Negative FISH analysis for t(11;14)(immunoglobulin heavy locus [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy) No prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal anti-body therapy for treatment of CLL or SLL Has met at least one of the following indications for treatment | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Non-Hodgkin's Lymphoma B-Cell ALL B-Cell CLL Group A: CD19+ B-ALL undergoing allogeneic HSCT or Group B: CD19+ B cell CLL or NHL undergoing allogeneic HSCT Life expectancy of ≥12 weeks Patient has an appropriate donor identified for hematopoietic stem cell transplantation Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT (Group A) OR any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic HSCT (Group B) Residual disease at the time of transplant (bulky or minimal) or post transplant relapse as evidenced by PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in the peripheral blood. MRD will be defined as detection in blood or marrow of any of the following Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the patient's leukemia cells pre transplant on a post transplant evaluation An immune globulin rearrangement known to be a disease marker for this patient post transplant A leukemia specific phenotype post transplant at a level of ≥ 0.01% Mixed donor chimerism (any level) Life expectancy ≥ 6 weeks Severe intercurrent infection Evidence of GVHD > grade II Pregnant or lactating History of hypersensitivity reactions to murine protein-containing products Currently taking corticosteroids (>0.5 mg/kg/day prednisone or equivalent) for therapy of GVHD | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Multiple Myeloma Patient ≥ 18 years old Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care Female patient is either post-menopausal or surgically sterilized or commits continued abstinence from heterosexual intercourse during the duration of the study or is willing to use two methods of birth control, one highly effective method and one additional effective method at the same time, at least 4 weeks before starting carfilzomib and bendamustine therapy, during carfilzomib and bendamustine therapy and for at least 4 weeks after stopping carfilzomib and bendamustine therapy. Highly effective methods are hormonal contraceptives (birth control pills, injections, and implants), intrauterine device, tubal ligation and partner's vasectomy. Additional effective methods are condom, diaphragm, and cervical cap. Women with child bearing potential must have two negative pregnancy tests (sensitivity at least 50 mIU/mL) prior starting carfilzomib and bendamustine therapy. The first pregnancy test must be performed 10 days and the second within 24 hours before starting carfilzomib and bendamustine therapy. Pregnancy testing for the first 4 weeks of study therapy must be performed weekly and thereafter every 4 weeks if menstrual cycles are regular or every 2 weeks if menstrual cycles are irregular Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study and for 6 months after stopping study therapy Patient with relapsed or/and refractory multiple myeloma after failure of two or more treatment regimens (previous bortezomib is allowed) Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein (M-protein) value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo or non-secretory MM with free light chains only in order to maximize interpretation of benefit results Pregnant or lactating females Patient has active infectious hepatitis type B or C or HIV Patients with active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention Peripheral neuropathy (PN) > CTCAE grade 2 and ≥ grade 2 painful PN (with the difference being in the of patients with Grade 2 painful PN) Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) Known history of intolerability to high dose dexamethasone Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and anti-platelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment Subject with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to baseline Patient has any other clinically significant illness that would, in the investigator's opinion, increase the patient's risk for toxicity Patient with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma of the skin, or in situ cancer of the cervix or breast, or localized prostate cancer of Gleason score <7 with a stable PSA) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Age 18 years or older Diagnosed CD20+ B chronic lymphocytic leukemia (CLL) according to National Cancer Institute (NCI) Active disease meeting at least 1 of the International Workshop on CLL (IWCLL) 2008 for treatment Refractory CLL (i.e. treatment failure or progression during treatment or within 6 months after the last treatment) or relapse CLL (i.e. participants who met for CR or PR, but progressed beyond 6 months post-treatment) At least 1 prior purine analogue or bendamustine containing therapy Life expectancy greater than (>) 6 months Use of effective contraception as described in the study protocol Prior Alogenic Bone Marrow Transplant Greater than or equal to (>/=) 3 previous lines of chemotherapy and/or immunotherapy for the CLL Previous obinutuzumab-containing regimen Treatment failure or progression within 6 months of bendamustine-containing regimen Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL; Richter's transformation) Patients with prolymphocytic transformation cannot entry the study either Active haemolytic anaemia Inadequate liver function History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with a history of malignancy that has been treated but not with curative intent will be excluded, unless the malignancy has been in remission without treatment for >/= 2 years prior to enrolment. Patients with a history of adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent are eligible Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Cardiovascular Disease Patients older than 18 years Literate Patient who agreed to participate in the study by signing the consent form at least 24 hours prior to surgery Patients with a history of surgery Patients in preoperative cardiac transplantation Patients who did not have at least two defining characteristics of the nursing diagnosis anxiety Patients using anxiolytics Smokers and / or patients who drank any amount of alcohol daily | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Tinnitus years of age History of chronic subjective tinnitus that cannot be attributed to vascular, neurologic, neoplastic or traumatic causes Capable of self-applying the lidocaine patches History of heart disease History of irregular heartbeat Prior MI Previous exposure to lidocaine as a treatment for tinnitus An allergy to adhesives Allergy to lidocaine Taking medications, herbal remedies and supplements that may interact with lidocaine, including but not limited to antivirals, benzodiazepines, and St. John's Wart Known liver disease Known kidney disease Adults who do not speak English | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 40.0-70.0, HIV Infection documented HIV infection between 40 and 70 years of age clinically stable HIV disease as evidenced by a CD4+ T lymphocyte count of > 250 cells/mm3 platelet count between 150,000 and 400,000 cells/mm3 to reduce bleeding risks associated with omega 3-fatty acids treatment with a stable HAART regimen for at least six months prior to study entry plasma HIV RNA < 75 copies/ml for at least 12 months elevated plasma concentration of hsCRP (> 2.0 mg/L) use within the past month of drugs (e.g., statins, steroids, hormones) and supplements (e.g., omega-3 fatty acids, glucosamine/chondroitin) that have anti-inflammatory effects (excluding non-regular use of aspirin or or medications or supplements that affect bleeding (e.g., heparin, warfarin, clopidogrel, garlic, ginseng) allergy to fish or shellfish chronic inflammatory condition (e.g., asthma, rheumatoid arthritis), opportunistic infection or cancer, renal impairment (serum creatinine > 2.0 mg/dL), thrombocytopenia (platelet count < 150,000/mm3), bleeding episodes (e.g., gum bleeding, nosebleeds), or a metabolic condition (e.g., diabetes mellitus, thyroid disease) body mass index of > 35, since obesity is associated with inflammation impaired liver function as evidenced by liver enzyme elevations > three times the upper limit of normal (AST or ALT > 150 IU/L) history of prostate cancer LDL cholesterol level > 120 mg/dL lifestyle factors use of illicit drugs and consumption of > 3 alcoholic drinks/day | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Cytopenia Patients with hematologic malignancies who have been subjected to allo-HSCT and that are diagnosed with one or more peripheral cytopenias with complete chimerism in bone marrow (determined by molecular-STR-studies). They may 1. Patients who have received as a source of cells MO or SP 2. Patients who have received cells from a related donor or unrelated HLA-matched 3. Patients transplanted with myeloablative or non-myeloablative conditioning Adequate cardiac function assessed from a clinical point of view by the researcher, with no history of ischemic heart disease (angina or myocardial infarction) in the previous 6 months Adequate pulmonary function assessed clinically without evidence of severe obstructive or restrictive lung disease Patients between 18 and 70 years Signed informed consent Patients whose haemopathy has not been controlled by the transplantation or is in progress at the time of treatment Patients who do not have complete chimerism in bone marrow (performed within 28 days prior to baseline by molecular study -STR-) Patients with thrombotic microangiopathy Patients with post-transplant cytopenias with toxic origin in relation to antiviral treatment (eg ganciclovir, valganciclovir) without concomitant graft against host disease Patients with bacterial, viral or fungal infection that is not being controlled with proper treatment Patients with a history of ischemic heart disease (angina or myocardial infarction) in the previous 6 months, and those considered by the investigator does not have adequate cardiac function, evaluated from a clinical point of view Patients with poor lung function, evaluated clinically, according to the researcher Patients who, in the opinion of the investigator, are not on a good position to tolerate treatment Patients who do not have the required donor Women pregnant or at risk of pregnancy by contraceptive measures inadequate | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Participants must meet the following on screening examination to be eligible to participate in the study Subjects must have CLL / SLL, as documented by a history at some point of an absolute peripheral blood B cell count > 5000, with a monoclonal B cell population co-expressing CD19, CD5, and CD23, or if CD23 negative, then documentation of the absence of t(11;14) or cyclin D1 overexpression. Alternatively patients with lymphadenopathy in the absence of circulating disease will also be eligible for this study if lymph node biopsy establishes the diagnosis of CLL with the above immunophenotype Participants must have measurable disease (lymphocytosis > 5,000, or palpable or CT measurable lymphadenopathy > 1.5 cm, or bone marrow involvement >30%) Subjects must not have received any prior systemic therapy for CLL and currently have an indication for treatment as defined by the IWCLL 2008 Guidelines Massive or progressive splenomegaly; OR Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR Grade 2 or 3 fatigue; OR Fever ≥ 100.5°F or night sweats for greater than 2 weeks without documented infection; OR Presence of weight loss ≥ 10% over the preceding 6 months; OR Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study Participants who have had any prior systemic therapy for CLL, or chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) for some other indication prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or idelalisib Subjects who have current active hepatic or biliary disease (with exception of participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study Other past or current malignancy that could interfere with the interpretation of outcome. Subjects who have been free of active malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or whose malignancy will not interfere with the interpretation of study results, are eligible Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae Known HIV positive. HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with idelalisib. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Richter's Transformation Richter's Transformation, arising in the setting of prior CLL, documented by histologically confirmed lymphoma, including large B-cell and immunoblastic variants All patients must have received at least one prior regimen for CLL, including cytotoxic chemotherapy, anti-CD20 monoclonal antibodies, a BTK inhibitor, or a PI3K inhibitor. Patients may have received high dose chemotherapy/autologous stem cell transplant (HDT/ASCT) or allogeneic hematopoietic stem cell transplant (allo SCT) One or more measurable (> 1.5 cm in longest dimension) disease sites on CT (preferably PET/CT) or, if CT is contraindicated, MRI (preferably PET/MRI) scans Objective documented evidence of disease progression at study entry Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1, except ibrutinib which may be continued until one day prior to initiation of selinexor; radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Patients must have recovered to Grade ≤ 1 from clinically significant adverse effects Prolymphocytic transformation Less than 1 month since completion of autologous stem cell transplantation or less than 3 months since completion of allogeneic stem cell transplantation Major surgery within 4 weeks of C1D1 Impairment of GI function or GI disease that could interfere with the absorption of selinexor, including obstructed GI tract and uncontrolled vomiting or diarrhea Inability or unwillingness to take supportive medications including a centrally acting appetite stimulant (e.g., mirtazapine or olanzapine) and a peripherally acting appetite stimulant (e.g., low dose glucocorticoids or megesterol acetate) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 50.0-80.0, Muscle Atrophy Quality of Life Age: between 50-80 years Primary TKA surgery Previous TKA and/or total hip arthroplasty surgery (older subjects). 2. Dementia or related mental issues that may potentially put the subject at risk as determined by the surgeon. 3. Untreated endocrine disease (Hypo/Hyperthyroidism, Addison's or Cushing's syndrome, etc.). 4. Significant heart, liver, kidney, blood, or respiratory disease. 5. Peripheral vascular disease. 6. Active cancer. 7. Recent (within 6 months) treatment with anabolic steroids. 8. Alcohol or drug abuse. 9. Inability to have MRI | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Liver Cirrhosis Signed written informed consent Dignosis of liver cirrhosis (clinical or by liver biopsy) Admission due to variceal bleeding occurred 5 to 42 days prior and standard treatment for secondary prophylaxis failed Confirmed splenorenal shunt, gastrorenal shunt or paraesophageal vein Sum of targeted SPSS diameters greater than half the diameter of portal vein Child-Pugh score ≤13 Hepatic carcinoma and/or other malignancy diseases Portal vein thrombosis (≥50% of the lumen) Budd-Chiari syndrome Other spontaneous portosystemic shunts Sepsis Spontaneous bacterial peritonitis Uncontrollable hypertension Serious cardiac or pulmonary dysfunction Renal failure With TIPS contraindications | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia confirmed diagnosis of CLL or SLL previously treated by low dose FCR for active disease requiring treatment per IWCLL dose reduction of fludarabine and cyclophosphamide due to age, comorbid conditions, or reduce creatinine clearance patients treated with low dose FCR within prospective clinical trials | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Ann Arbor Stage III Small Lymphocytic Lymphoma Ann Arbor Stage IV Small Lymphocytic Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Small Lymphocytic Lymphoma Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; previously treated, pathologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that requires as per the National Cancer Institute (NCI) Working Group Guidelines for the treatment of CLL; the diagnosis of CLL is defined by the presence of 5 x 10^9 clonal B-lymphocytes/L in the peripheral blood; clonality of the lymphocyte population is established with flow cytometry and the demonstration of the following surface markers: CD5, CD23, CD19, CD20 and the presence of either kappa or lambda immunoglobulins; the diagnosis of SLL may be made with the demonstration of < 5 x 10^9 clonal B-lymphocytes/L in the peripheral blood, with the clinical or radiographic features of enlarged lymph nodes or organomegaly, and the demonstration of SLL cells in the lymph node biopsy; institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression; patients may not have had a history of Richter's transformation No prior systemic therapy for CLL or SLL including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy), radiation therapy, within 4 weeks of enrollment; no prior carmustine (BCNU) or mitomycin C within 6 weeks of enrollment; no radioimmunotherapy within a year of enrollment; no corticosteroids administered within 2 weeks prior to study entry, except for maintenance therapy (=< prednisone 20 mg daily or equivalent) for a non-malignant disease Patients may have had a prior autologous stem cell transplant; no prior history of allogeneic stem cell transplant Patients may have received prior lenalidomide as long as it has been at least two years since exposure and the patient may not have experienced a progression while receiving lenalidomide previously No Bruton's tyrosine kinase inhibitor at any point prior to enrollment No history of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib, lenalidomide or rituximab or hypersensitivity to murine proteins or to any component of rituximab Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable the following Bone lesions (lesions if present should be noted) Ascites Pleural/pericardial effusion Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 6 weeks prior to first administration of study treatment Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib Patients who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or patients who require continuous treatment with a strong CYP3A inhibitor Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or an infection requiring systemic antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; recent infections requiring systemic treatment need to have completed therapy > 14 days before the first dose of study drug Pregnant and breastfeeding women are excluded from this study; pregnant women are excluded in this study because ibrutinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib, breastfeeding should be discontinued if the mother is treated with ibrutinib Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible; unless the patient's CD4 count is below the institutional lower limit of normal Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug Presence of transfusion-dependent thrombocytopenia | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Metastatic Pancreatic Adenocarcinoma Stage III Pancreatic Cancer AJCC v6 and v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Unresectable Pancreatic Carcinoma PHASE I STUDY - ARM A (DOSE LEVEL 1) AND ARM B (DOSE LEVEL 2) Patients must have histologically or cytologically confirmed metastatic or unresectable locally advanced adenocarcinoma of the pancreas with no prior systemic therapy for metastatic or locally advanced disease Previous neo-adjuvant or adjuvant treatment is allowed provided that it was given >= 6 months prior to registration Patients must NOT be receiving any other investigational agents concurrently and must not have received any other investigational agents =< 4 weeks prior to registration Patients must not have a pre-existing > grade 1 motor or sensory neuropathy Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, gemcitabine or AZD1775 Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients must have a life expectancy of >= 12 weeks Patients may have had prior radiotherapy for metastatic disease as long as it was > 4 weeks prior to registration and the patient has recovered from adverse events associated with the radiotherapy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Chronic Lymphocytic Leukemia Clinical and phenotypic verification of B cell CLL and measurable disease. Immunophenotyping of the leukemic cells must demonstrate a monoclonal B cell population with immunophenotype consistent with CLL Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of therapy, or a 50% increase of baseline disease measurements after achieving a clinical response Not amenable to approved therapies Prior Therapy: Must have progressed after purine-analog or alkylator based therapy, or be considered inappropriate for chemo-immunotherapy due to one of the following Del 17p, which is associated with poor response to chemo-immunotherapy, or Age greater than 70, or Age greater than 65 with one of the following Grade ≥ 3 neutropenia, anemia, or thrombocytopenia attributable to cumulative myelotoxicity from prior administration of cytotoxic agents (as documented by bone marrow biopsy obtained since last prior therapy), or Clinically apparent autoimmune cytopenia which may be exacerbated by fludarabine therapy, or Estimated creatinine clearance (eCCr) <70 mL/min (as determined by the Cockcroft-Gault method), or Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies Patients who are currently receiving another investigational agent are excluded Patients who have had chemotherapy (e.g., purine analogues, alkylating agents), immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of initiation of UC-961 or at any time during the study Patients who have had prior (within 8 weeks of initiation of UC-961) or concurrent antibody therapy directed against CLL (i.e., Rituxan® and Campath®) Current infection requiring parenteral antibiotics Active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) Concurrent malignancy or prior malignancy within the previous 3 years (other than completely resected carcinoma in situ, prostate cancer, or localized non-melanoma skin cancer) Known central nervous system (CNS) involvement by malignancy Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia Uncompensated hypothyroidism (defined as thyroid-stimulating hormone (TSH) greater than 2x upper limit of normal not treated with replacement hormone) | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 16.0-999.0, Cellulitis Age >16 years Suitable for treatment with flucloxacillin 500mg -1gram qds monotherapy or a suitable alternative for penicillin allergic patients as listed in the local prescribing guidelines Appearance of typical, plaque-like area of erythema over any body part excluding the perineum within the preceding 5 days with any 2 of the following signs Increased warmth over affected area Swelling of affected area Pain over affected area Regional lymphadenopathy Requirement for IV antibiotics as decided by the treating clinician Age less than 16 years No telephone or access to a telephone Abscess alone without co-existing signs of cellulitis Mammalian bite wounds Infected diabetic foot ulcer Necrotising soft tissue infections Perineal cellulitis Suspected septic arthritis or osteomyelitis Decubitus ulcers | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocyte Leukemia Adult Patients 18 years of age or older. 2. Diagnosis of CLL meeting IWCLL criteria. 3. The diagnosis of CLL requires a history of lymphocytosis with a B-lymphocyte count ≥5,000/μL. Prolymphocytes may comprise no more than 55% of blood lymphocytes. 4. Active disease meeting at least 1 of the following IWCLL 2008 for requiring treatment: 1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia or thrombocytopenia. 2. Massive (ie, at least 6 cm below the left costal margin), progressive, or symptomatic splenomegaly. 3. Massive nodes (ie, at least 10 cm in longest diameter), progressive, or symptomatic lymphadenopathy. 4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time (LDT) of less than 6 months (which may be extrapolated). Lymphocyte doubling time can be obtained by linear regression extrapolation of ALCs obtained at intervals of 2 weeks over an observation period of 2 to 3 months. For patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded. 5. Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs Unintentional weight loss >10% within the previous 6 months prior to screening Significant fatigue (inability to work or perform usual activities) Fevers higher than 38.0°C for 2 or more weeks without evidence of infection; or Night sweats for more than 1 month without evidence of infection Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as at least one lymph node >1.5 cm in longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended. 5. No prior treatment. 6. Total CIRS >6 and/or creatinine clearance <70 ml/min [Cockcroft-Gault]). 7. Hematology values within the following limits: Absolute neutrophil count (ANC) ≥1 x 109/L (ie, ≥1000/μL) independent of growth factor support. Platelets ≥50,000/mm3 if bone marrow involvement independent of transfusion support 8. Biochemical values within the following limits: 1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) 2. Total bilirubin ≤1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin 3. Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault) ≥40 mL/min 9. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree not to donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug. 10. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. 11. A signed (or signed by their legally-acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study Any significant concurrent, uncontrolled medical condition or organ system dysfunction and/or laboratory abnormality or psychiatric disease which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk or prevent the subject from signing the informed consent form. 2. Pregnant or lactating females 3. Known presence of alcohol and/or drug abuse. 4. Any potential subject who meets any of the following will be excluded from participating in the study. 5. Major surgery within 4weeks of randomization. 6. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia. 7. Known central nervous system lymphoma. 8. History of stroke or intracranial hemorrhage within 6 months prior to randomization, or of a significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae. 9. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) in any moment of the study. 10. Requires treatment with strong CYP3A inhibitors. 11. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association 12. Vaccinated with live, attenuated vaccines within 4 weeks of randomization. 13. Known history of human immunodeficiency virus (HIV) positive serology for HIV; active Hepatitis B Virus infection or positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg and HBV-DNA; active Hepatitis C or HCV-RNA positive; any uncontrolled active systemic infection requiring intravenous (IV) antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection; history of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months. 14. Richter's syndrome (RS), concomitant or past malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-65.0, Chronic Lymphocytic Leukemia Leukemia Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma. as per IW-CLL 2008 criteria. Patients must also require therapy for that diagnosis, based on meeting at least one of the following evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 10^9/L) massive (≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of <6 months. Lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of <30 x 10^9/L, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy documented constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs unintentional weight loss >10% within 6 months prior to screening significant fatigue (inability to work or perform usual activities) fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection Concurrent Conditions History of other malignancies, except Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >20 mg/day of prednisone) within 28 days of the first dose of study drug Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug Known bleeding disorders (eg, von Willebrand's disease) or hemophilia History of stroke or intracranial hemorrhage within 6 months prior to enrollment | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Myelodysplastic Syndromes Completion of the treatment period in the base study A536-03 (ClinicalTrials.gov Identifier: NCT01749514) Adequate birth control measures Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements Patient understands and is able to provide written informed consent. In addition, patients with treatment interruption (defined as patients who complete their end-of-study visit in A536-03 and cannot directly roll over to A536-05) must also meet the following Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) 2 (white blood count (WBC) < 13,000/μL) that meets International Prognostic Scoring System (IPSS) classification (Appendix 2) of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening Anemia defined as Mean hemoglobin concentration < 10.0 g/dL of 2 measurements (one performed within one day prior to Cycle 1 Day 1 and the other performed 7-28 days prior to Cycle 1 Day 1), for non-transfusion dependent (NTD) patients (defined as having received ˂ 4 units of red blood cells (RBCs) within 8 weeks prior to Cycle 1 Day 1), OR Transfusion Dependent (TD), defined as having received ≥ 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1 Platelet count ≥ 30 x 109/L Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia) Discontinuation/withdrawal from the base study A536-03 (due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication [e.g. azacitidine], medical reason or adverse event (AE), hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up) prior to completion of the treatment period Prior treatment with azacitidine or decitabine Treatment within 28 days prior to Cycle 1 Day 1 with an erythropoiesis-stimulating agent (ESA) Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) Lenalidomide Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1 Treatment with another investigational drug (including sotatercept [ACE-011]) or device, or approved therapy for investigational use ≤ 28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1 Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Prolymphocytic Leukemia Recurrent Mantle Cell Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Richter Syndrome World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Life expectancy >= 2 months Appropriate histologic diagnosis (a) or (b) (a) Histologically documented diagnosis of intermediate or high risk CLL/SLL, B-PLL, and RT arising from CLL/SLL according to the 2008 guidelines, meeting for active disease requiring treatment Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia) Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy Constitutional symptoms including any of the following Unintentional weight loss of 10% or more within 6 mos Prior therapy as follows Major surgery within 2 weeks Corticosteroids greater than 20 mg/day prednisone (or equivalent) within 2 weeks unless used by inhalation or topical route, or unless necessary for premedication before iodinated contrast dye, or for autoimmune hemolytic anemia Cytotoxic chemotherapy or biologic therapy within 4 weeks, excepting BCR kinase inhibitors for which no wash out is required, or Nitrosoureas within the 6 weeks of the planned first dose of the study drug Failure to recover toxicity from prior chemo or radiotherapy to grade 1 Known active leukemia or lymphoma of the central nervous system (CNS) requiring therapy Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: absolute neutrophil count (ANC) < 1 x 10^9/L Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: platelets < 30 x 10^9/L | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Hodgkin Disease Non-Hodgkin Lymphoma Severe Chronic Active Epstein Barr Virus T/NK-lymphoproliferative Disease Nasopharyngeal Carcinoma Smooth Muscle Tumor Any patient regardless of age or sex, with diagnosis of either EBV positive Hodgkin's lymphoma EBV Positive non-Hodgkin's Lymphoma (regardless of histologic subtype) EBV (associated)-T/NK-lymphoproliferative disease Severe Chronic Active EBV (CAEBV) - CAEBV is defined as patients with high EBV viral load in plasma or PBMC (>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV Other EBV positive malignancies (e.g. nasopharyngeal carcinoma, smooth muscle tumors, etc.) AND in first or subsequent relapse (Group A) with active disease persisting despite therapy (Group B) with active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group C) 2. EBV positive tumor 3. Weighs at least 12kg 4. Informed consent (and assent as applicable) obtained from patient/guardian. 1. Any patient regardless of age or sex, with diagnosis of either Pregnant or lactating 2. Severe intercurrent infection 3. Current use of systemic corticosteroids more than 0.5 mg/kg/day 4. Patients receiving ATG, Campath, or other immunosuppressive T cell monoclonal antibodies within 30 days | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Prolymphocytic Leukemia Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia A histologically confirmed diagnosis of CLL according the International Workshop on CLL/SLL/B-cell PLL or variant of these (IWCLL or World Health Organization [WHO] Criteria) and meet for treatment or have need for cytoreduction for stem cell transplantation or alternative cell therapy; OR A histologically confirmed diagnosis of mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL) de novo or in the setting of transformation from an indolent lymphoma (including DLBCL not otherwise specified) according to the World Health Organization for diagnosis of NHL; AND Patients must have received at least one prior therapy for CLL or NHL, need additional treatment, and meet for relapsed or refractory disease; they may not be a candidate for curative therapy; relapsed disease is defined as a patient who previously achieved a complete remission (CR) or a partial remission (PR), but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic or anti-lymphoma therapy, or any response less than a CR or PR Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Patients with NHL must have objective, documented evidence of disease prior to study entry Platelet count >= 50,000/mm^3 in the absence of bone marrow involvement; patients with bone marrow involvement only require a platelet count of 30,000/mm^3 Absolute neutrophil count >= 1000/mm^3 in the absence of bone marrow involvement Creatinine clearance (as calculated by Cockroft Gault equation = [140-age] * mass [kg]/[72 * creatinine mg/dL) >= 30mL/min Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN) Total bilirubin =< 2.0 x ULN Patients who are concurrently receiving any other investigational agents Patients who have received Radiation or chemotherapy =< 4 weeks Mitomycin C, nitrosureas, or radio-immunotherapy =< 6 weeks, or Immunotherapy or targeted therapy (such as kinase inhibitors) =< 2 weeks prior to cycle 1 day 1(except patients already on ibrutinib) Palliative steroids for disease related symptoms are allowed as long as dose is tapered down to an equivalent of =< 10 mg of oral prednisone daily on cycle 1 day 1 Patients who have underwent autologous or allogeneic stem cell transplant =< 4 weeks prior to cycle 1 day 1 or have active graft-versus-host disease are excluded Patients unable to swallow capsules, those with uncontrolled vomiting or diarrhea or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as: malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine Patients who are 20% below their ideal body weight Patients must not be receiving systemic anticoagulation with warfarin; patients must be off warfarin for 30 days prior to enrollment; patients who require anticoagulation with an agent other than warfarin will not be excluded, but must be reviewed by the principal investigator prior to enrollment | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Monoclonal B-Cell Lymphocytosis Stage 0 Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia Stage I Small Lymphocytic Lymphoma Diagnosis of: 1. CLL according to the National Cancer Institute (NCI) 2. Small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) 3. MBL according to the consensus This includes previous documentation of Biopsy-proven small lymphocytic lymphoma or Diagnosis of CLL or MBL as evidenced by all of the following Clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL defined as The population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc) Clonality as evidenced by k (kappa) or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis) NOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL Patients with a peripheral blood B-cell lymphocyte count of < 5 x 10^9/L and no evidence of lymphadenopathy or organomegaly will be classified as MBL; patients with a peripheral blood B-cell lymphocyte count of < 5 x 10^9/L who have evidence of lymphadenopathy will be classified as SLL; patients with a peripheral blood B-cell lymphocyte count >= 5 x 10^9/L will be considered to have CLL Before diagnosing MBL, CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/cyclin D 1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy CLL or SLL patients only (does not apply to MBL patients): Rai stage 0-1 (both CLL and SLL patients can be staged using the Rai system) Palpable lymph nodes > 3 cm in maximal dimension Any of the following Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Any of the following comorbid conditions New York Heart Association classification III or IV cardiovascular disease Recent myocardial infarction (=< 30 days) Uncontrolled infection Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Advanced Solid Tumors Chronic Lymphocytic Leukemia Advanced solid tumors likely to have alterations in DNA repair mechanisms, such as the BRCA and ATM pathways, or CLL, with no other standard surgical, radiation, or systemic anticancer therapies available. Subjects with CLL will be enrolled in 1 of the RP2D expansion cohorts only Tumor accessible for biopsies and agree to pretreatment tumor biopsy Measurable or evaluable disease in accordance with v 1.1 for solid tumors or Cheson´s for CLL Male or female subjects at least 18 years of age who sign written informed consent Other protocol-defined could apply Eastern Cooperative Oncology Group performance status > 1 Prior treatment with chemotherapy, immunotherapy, hormonal therapy, with the exception of luteinizing hormone releasing hormone (LHRH) analogs, biologic therapy, any other anticancer therapy, or any other investigational agent within 28 days of the first dose of MSC2490484A (6 weeks for nitrosoureas or mitomycin C) Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone marrow/stem cell transplantation within 5 years of study start. The extent of previous radiotherapy to the bone marrow will be determined by the investigator Receiving medications or herbal supplements that are known to be potent inhibitors of cytochrome P450 3A4 or inducers of cytochrome P450 3A4 Not recovered from toxicity due to prior therapy to baseline or an AE CTCAE Grade of 1 or less (except alopecia) Poor vital organ function as defined in the protocol Significant cardiac conduction abnormalities as defined in the protocol Central nervous system metastases unless previously radiotherapy treated, stable by computerized tomography (CT) scan for at least 3 months without evidence of cerebral edema, and no requirements for corticosteroids or anticonvulsants Other protocol-defined could apply | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leucemia Diagnosis of CLL in need of treatment according to the iwCLL guidelines 2. Relapsed or refractory disease after at least one, but no more than 3 prior regimens for CLL 3. Medically fit patients without relevant comorbidity, defined as total CIRS score ≤6 (single score < 4 for one organ category) 4. ECOG performance status of 0 5. Hematology values within the following limits unless cytopenia is caused by the underlying disease, i.e. no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome (MDS), hypoplastic bone marrow due to toxicity of prior therapy): 1. Absolute neutrophil count ≥1.5 x 109/L 2. Platelets ≥50 x 109/L and more than 7 days since last transfusion 6. Creatinine clearance >60 ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24 h urine collection 7. Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 the institutional ULN value, unless directly attributable to the patient's CLL 8. Negative serological Hepatitis B test (i.e. HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative); negative testing of Hepatitis C RNA; negative HIV test within 6 weeks prior to registration 9. 18 years of age or older 10. Life expectancy >6 months 11. Able and willing to provide written informed consent and to comply with the study protocol procedures Detected del(17p) or TP53 mutation 2. Refractoriness to FCR / BR 3. Transformation of CLL to aggressive NHL (Richter's transformation) 4. Known central nervous system (CNS) involvement 5. Evidence of significant uncontrolled concomitant disease 6. Major surgery < 30 days before screening 7. Decompensated hemolytic anemia 28 days before screening 8. Hemolytic cystitis 28 days before screening 9. Patients with a history of confirmed PML 10. Prior treatment with GA101 11. History of prior malignancy, except for conditions as listed below (a-d) and if patients have recovered from the acute side effects incurred as a result of previous therapy: 1. Malignancies treated with curative intent and with no known active disease present for ≥ 2 years before registration 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease at screening 3. Adequately treated cervical carcinoma in situ without evidence of disease at screening 4. Surgically adequately treated low grade, early stage localized prostate cancer without evidence of disease at screening 12. Use of investigational agents or concurrent anticancer treatment within the last 4 weeks before registration 13. Patients with active infection requiring systemic treatment 14. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies and/ or known hypersensitivity to any constituent of the product 15. Hypersensitivity to fludarabine, cyclophosphamide, bendamustine, GA101 and/ or to any of the excipients for example mannitol 16. An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive an intensive therapy for CLL 17. Legal incapacity 18. Women who are pregnant or lactating 19. Fertile men or women of childbearing potential unless: 1. surgically sterile or ≥2 years after the onset of menopause 2. willing to use a highly effective contraceptive method (Pearl Index <1) such as those listed at section 4.2.2 during study treatment and for 12 months after end of study treatment 20. Vaccination with a live vaccine within a minimum of 28 days before screening 21. Participation in any other clinical trial which would interfere with the study drug 22. Prisoners or subjects who are institutionalized by regulatory or court order 23. Persons who are in dependence to the sponsor or an investigator | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lung Cancer Patients must have histologically or cytologically confirmed stage IV non-small cell lung cancer, or recurrent non-small cell lung cancer which is not amenable to curative intent therapy. 2. Patients must have measurable disease by Response Evaluation in Solid Tumors(RECIST) 1.1 3. For EGFR mutant cohort, patients must have: a) Documented EGFR mutation by Clinical Laboratory Improvement Amendments (CLIA)-certified test b) Documented disease progression on treatment with erlotinib, gefitinib, afatinib, or other EGFR-targeted tyrosine kinase inhibitor c) Tissue available from a biopsy or surgical procedure performed after progression on an EGFR targeted tyrosine kinase inhibitor. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy. 4. For HER2 mutant cohort, patients must have: a) Documented EGFR mutation by CLIA-certified test b)Documented disease progression on treatment with erlotinib, gefitinib, afatinib, or other EGFR-targeted tyrosine kinase inhibitor c)Tissue available following progression on most recent systemic therapy. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy. 5. Age >/=18 years 6. Eastern Cooperative Oncology Group (ECOG) performance status </=2 7. Ability to take pills by mouth 8. Patients must have normal organ and marrow function as defined: leukocytes >/= 3,000/mcL; absolute neutrophil count >/= 1,500/mcL; hemoglobin >/= 9 g/dL; total bilirubin </= 1.5 x institutional upper limit of normal (ULN); AST(SGOT)/ALT(SGPT) </= 2.5 × ULN or </= 5 x ULN if metastases to the liver; creatinine clearance >/= 45 mL/min 9. Patients with asymptomatic brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids. Maximum daily dose of steroids should be prednisone 20 mg or equivalent. Radiation therapy for brain metastases must be completed at least 14 days prior to treatment on protocol 10. The effects of ibrutinib on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use highly effective contraception (if using hormonal birth control must add a second barrier method; abstinence) prior to study entry, for the duration of study participation as well as for at least 1 month after the last dose of ibrutinib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use highly effective contraception prior to the study, for the duration of study participation and 3 months after completion of ibrutinib administration. 11. Ability to understand and the willingness to sign a written informed consent document Patients who have received EGFR tyrosine kinase inhibitors within 72 hours of initiation of study treatment, or treatment with other anti-cancer agents within 21 days of study treatment 2. Prior treatment with ibrutinib 3. Known hypersensitivity to ibrutinib 4. Concurrent use of agents that strongly inhibit or induce CYP3A unless use is approved by the medical monitor 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 6. Pregnant and nursing women 7. Patients with a history of another active malignancy within the past two years, with the exception of non-melanoma cutaneous malignancy, cervical carcinoma in situ, or ductal carcinoma in situ which has been successfully treated with curative intent therapy 8. Any gastrointestinal disorder expected to limit absorption of ibrutinib 9. Treatment with warfarin or other vitamin K antagonist. Patients with using warfarin who switch to another form of anticoagulation will be eligible 10. Patients with persistent and uncontrolled atrial fibrillation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Lymphoplasmacytic Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Nodal Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Recurrent Splenic Marginal Zone Lymphoma Recurrent Waldenstrom Macroglobulinemia Refractory B-Cell Non-Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Refractory Follicular Lymphoma Refractory Lymphoplasmacytic Lymphoma Refractory Nodal Marginal Zone Lymphoma Refractory Small Lymphocytic Lymphoma Refractory Splenic Marginal Zone Lymphoma Refractory Waldenstrom Macroglobulinemia Richter Syndrome Waldenstrom Macroglobulinemia CLL/SLL (ARM A) ONLY Diagnosis of CLL according to the National Cancer Institute (NCI) or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of Biopsy-proven small lymphocytic lymphoma or Diagnosis of CLL according to NCI working group as evidenced by all of the following Peripheral blood B cell count of > 5 x 10^9/L consisting of small to moderate size lymphocytes Immunophenotyping consistent with CLL defined as The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression] or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.) Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis) NOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis for t(11;14) (immunoglobulin H [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy Currently participating in or has participated in a study of an investigational agent or using an investigational device =< 28 days prior to registration Receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy =< 7 days prior to registration Low doses of steroids (=< 20 mg of prednisone or equivalent dose of other steroid/day) Previous use of corticosteroids is allowed After initiation of MK-3475 therapy, steroid can be used for management of potential immune mediated adverse events (AE) for less than 8 weeks of therapy Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted Prior anti-cancer monoclonal antibody =< 28 days prior to registration or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier Prior chemotherapy or radiation therapy =< 14 days prior to registration or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Men and women 18 years of age and older with histologically confirmed disease Active disease as defined by at least one of the following (IWCLL consensus criteria) Weight loss ≥10% within the previous 6 months Extreme fatigue Fevers of greater than 100.5ºF for ≥2 weeks without evidence of infection Night sweats for more than one month without evidence of infection Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive or progressive splenomegaly Massive nodes or clusters or progressive lymphadenopathy Progressive lymphocytosis with an increase of >50% over a 2 month period, or an anticipated doubling time of less than 6 months Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or investigational products in the last 4 weeks Richter's transformation. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy. Impaired hepatic function | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-49.0, West Nile Viral Infection Age >/=18 years and < 50 years 2.Able to read, sign, and date the informed consent document 3. Available and willing to participate for the planned duration of the study 4.Are in good health, as judged by the investigator and determined by vital signs, medical history, and physical examination 5.Sexually active males must agree to use a medically acceptable form of contraception* in order to be in this study and must agree to continue such use until day 30 after the last vaccination.Medically acceptable contraceptives (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. 6.Women of childbearing potential* must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each vaccination *Not sterilized via tubal ligation, bilateral oophorectomy, or hysterectomy and still menstruating or < 1 year of the last menses if menopausal 7. Women of childbearing potential must have used an acceptable method of contraception* in the 30 days prior to enrollment and must agree to continue such use until day 30 after the last vaccination. *Includes, but is not limited to, abstinence from sex with men,barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing®, successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure, and licensed hormonal methods such as implants, injectables, or oral contraceptives Any clinically significant acute or chronic medical condition* or need for chronic medications** that, in the opinion of the investigator, will interfere with immunity or affect safety *Includes, but is not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions ** Receipt of systemic, prescription medications for the treatment of chronic medical conditions or variations of normal physiologic functions are permissible if, in the opinion of the investigator, they are used for conditions that are not clinically significant and would not impact the safety of the subject or the safety and immunogenicity outcomes of the protocol. Use of systemic, over-the-counter medications and PRN systemic, prescription medication are allowed if, in the opinion of the investigator, they pose no additional risk to subject safety or assessment of immunogenicity/reactogenicity. Topical (except corticosteroid) medications, nasal (including corticosteroid) medications, vitamins, and supplements are permissible 2. Asthma, other than mild, well-controlled asthma* *Cold or exercise induced asthma controlled with inhaled medications other than inhaled corticosteroids is permissible. Participants should be excluded if they require daily bronchodilator use, or have had an asthma exacerbation requiring oral/parenteral steroid use or have used theophylline or inhaled corticosteroids in the past year 3. Diabetes mellitus 4. Unstable depression or bipolar disorder* *Has received <3 months of the same anti-depressant or bipolar disorder medication(s) (and dose) or has had a decompensating event during the previous 3 months or has depression or bipolar disorder that in the opinion of the investigator will compromise the subject's ability to comply with protocol requirements 5. Unstable seizure disorder (defined as requiring medication for seizure control or with seizure activity within the past 3 years) 6. Autoimmune disease (lupus, multiple sclerosis, rheumatoid arthritis, autoimmune thyroid disease, etc.); vitiligo, and mild eczema or mild psoriasis not requiring chronic therapy are permissible. 7. Known or suspected congenital or acquired immunodeficiency including anatomic or functional asplenia or immunosupppression as a result of underlying illness or treatment 8. Abuse of alcohol or drugs that, in the opinion of the investigator, may interfere with the subject's ability to comply with the protocol 9. Unstable hypertension (well-controlled hypertension with medication is permissible) 10. Body mass index (BMI) >/= 35 11. Known allergy to components of the study product .Including the following: aluminum hydroxide, sorbitol, potassium chloride, sodium chloride 12. Seropositive to West Nile virus 13. History of a visit to South America or sub-Saharan Africa lasting one month or more 14. History of military service 15. History of vaccination against yellow fever, tick-borne encephalitis, or Japanese encephalitis 16. History of vaccination with West Nile virus candidate vaccines. 17. Attended primary (grade) school in Austria, Germany, Japan, South Korea, India, Thailand, Nepal, Vietnam, or Taiwan (where tick-borne encephalitis vaccine is given) 18. History of dengue fever or receipt of a dengue fever vaccine 19. Active neoplastic disease* *Participants with a history of malignancy may be included if treated by surgical excision or if treated by chemotherapy or radiation therapy has been observed for a period that in the investigator's estimation provides a reasonable assurance of sustained cure (not less than 36 months) 20. Chronic topical or systemic corticoste roid use* *Corticosteroid nasal sprays for allergic rhinitis are permissible. Persons using a topical corticosteroid for a limited duration for mild uncomplicated dermatitis such as poison ivy or contact dermatitis may be enrolled the day after their therapy is completed. Oral or parenteral (intravenous, subcutaneous or intramuscular) corticosteroids given for non-chronic conditions not expected to recur are permissible if, within the year prior to enrollment, the longest course of therapy was no more than 14 days and no oral or parenteral corticosteroids were given within 30 days prior to enrollment. Intraarticular, bursal, tendon, or epidural injections of corticosteroids are permissible if the most recent injection was at least 30 days prior to enrollment. 21. Are breastfeeding or plan to breastfeed at any time throughout the study 22. Receipt or planned receipt of inactivated vaccine or allergy desensitization injection 14 days before or after a study vaccination 23. Receipt or planned receipt of live attenuated vaccine 30 days before or after a study vaccination 24. Receipt of any other experimental agent within 30 days prior to vaccination or planned receipt prior to the end of the study 25. Plans to enroll in another clinical trial* that could interfere with safety assessment of the investigational product at any time during the study period *Includes trials that have a study intervention such as a drug, biologic, or device 26 Receipt of blood products or immunoglobulin within six months prior enrollment 27. Donation of a unit of blood within 56 days prior to enrollment or intends to donate blood during the study period 28. Systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg 29.Resting heart rate <40 or >100 beats per minute 30.Oral temperature >/= 38 degrees C (100.4 degrees F) 31.Positive serology for HIV 1/2* *If the enzyme linked immunosorbent assay (ELISA) is positive, HIV confirmation should be performed. If the HIV Western Blot is not consistent with HIV infection, the volunteer may be enrolled. A past participant in an HIV vaccine trial who has a positive antibody ELISA may participate if the Western Blot is not consistent with pending seroconversion or positive or an HIV polymerase chain reaction (PCR) assay result is below the level of detection of HIV. 32. Positive hepatitis B surface antigen (HBsAg) 33. Positive antibody to hepatitis C virus (HCV) 34. Any Grade 1 or higher screening clinical lab value* (see Toxicity Table Appendix B) *Screening clinical labs blood tests (white blood cell [WBC] count, hemoglobin level, platelet count, creatinine, blood urea nitrogen, non-fasting glucose, potassium, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and total bilirubin) and urine tests (protein, glucose). 35. Plan to have a major change in exercise routine from 72 hours before any dose of study vaccine/placebo through 15 days after that dose 36. Acute febrile illness (oral temperature >/= 38 deg | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Diffuse Large B-cell Lymphoma The patient must, at the investigator's opinion, be able to meet all requirements of the clinical trial. 2. Patients must give voluntarily informed consent before performing any test test that is not part of routine care of patients. 3. Age between 18 and 70 years. 4. Candidate for treatment with high-dose QT and HSCT . 5. Diffuse large B-cell lymphoma (LDCGB) histological diagnosis according to the WHO classification ( see Annex 8). 6. Refractory lymphoma or relapsed after 1st line treatment consisting of rituximab combined with a regimen of chemotherapy (CT scan ) including anthracyclines. : Relapse is defined as recurrence of lymphoma after obtaining complete response (RC) with 1st line treatment . In these cases, LDCGB histologic confirmation at the time of relapse is recommended Refractory lymphoma be considered if it meets one of the following : partial response after at least 6 cycles of 1st line regimen . They may also patients in partial response after 4 cycles if the researcher believes that the response is suboptimal, and patients with stage I II if they have received 3 cycles of R QT + affection field radiotherapy . stable disease after at least 3 cycles of 1st line regimen . progression during treatment of 1st line , defined as response for malignant lymphoma 2007 (see Annex 9) 7. CT scan evidence of at least two clearly demarcated lesions with a diameter of 1.5 cm, or 1 well-defined lesion with a diameter > 2 cm . 8. Evidence of positive lesions by PET, coincident with the anatomical areas affected by CT scan . 9. Eastern cooperative oncology group performance status (ECOG) less than or equal to 2. 10. Resolution of toxicities caused by the 1st line regimen to less than or equal to grade 1. 11. Women of childbearing age ( see Appendix 12) must: Obtain a negative pregnancy test before starting medically supervised therapy study. Must accept continuing pregnancy tests conducted during the course of the study and after the end of study therapy . This applies even if the patient practices complete and continued abstinence . They must either commit to continued abstinence or heterosexual sex (which should be reviewed monthly ) or agree to use and be capable of complying with effective contraception without interruption, 28 days before starting the study drug during the study therapy (including during periods of dose interruptions ) , and for 28 days after discontinuation of study therapy . 12 male patients ( see Appendix 12) must Accept to use a latex condom during any sexual relations with women of childbearing potential , even if they have had a vasectomy , while participating in this study, during dose interruptions and after discontinuation of treatment Accept refrain from donating sperm while participating in this study and for a time after cessation of treatment (see specific data ) . 13. All patients must: Understand that the study drug could potentially have a teratogenic risk . Agree to abstain from donating blood while they are taking the treatment and after discontinuation of study drug therapy . Agree not to share study medication with anyone else. For advice on precautions against pregnancy and potential risks of fetal exposure Patients that previously received any antitumor agent for the treatment of LDCGB except : I ) rituximab in combination with regimen including anthracyclines II ) radiotherapy as part of first-line treatment . 2 Previously received any of the following treatments in the 28 days prior to the test regime : I ) antitumor chemotherapeutic agents ; II ) radiotherapy , unless limited to a maximum dose of < or =10 Gy to control severe life-threatening symptoms ; III ) glucocorticoid except equivalent doses < or = 1 mg / kg of prednisolone / day with duration < or = 7 days; iv ) any therapeutic agent under investigation. 3. Known involvement of the central nervous system (CNS) by lymphoma. 4. Presence of abnormal or clinically significant cardiac disease, such as acute myocardial infarction or unstable angina within 6 months prior to initiation of treatment with LR ESHAP , grade III or IV heart failure, uncontrolled hypertension or history of poor compliance with antihypertensive treatment , uncontrolled treated arrhythmias, except , with the exception of extra systoles or minor conduction abnormalities. 5. Any other serious or uncontrolled medical condition , such as diabetes, uncontrolled active infection, significant cerebrovascular disease, poorly controlled psychiatric disease, etc. . 6. Known or suspected hypersensitivity to any of the agents of the treatment under evaluation. 7. Presence of any limitations that compromise the patient's ability to comply with treatment . 8. Positive serology for HIV or Hepatitis B Virus (HBV) surface antigen (HBsAg ) . If negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the subject will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included 9. Active Hepatitis C (RNA positive serum) . If RNA positive result would the patient from the trial in cases of patients with positive serology for Hepatitis C Virus (HCV). If the load ( RNA ) were HCV negative patients could be included in the study. 10. Prior history of malignancy other than to LDCGB (except basal or squamous cell skin and in situ carcinoma of the cervix or breast ) unless the patient free of disease beyond 5 years are. 11 Changes in laboratory values ??that might involve unacceptable risks or compromise compliance with the protocol , including: platelets < 50 x 109 / L or neutrophils <1 x 109 / L , unless attributed to infiltration by lymphoma bone marrow (MO) . or creatinine > 1.5 times the normal upper limit . or Total bilirubin > 2 times the upper limit of normal or alanine aminotransferase (ALT) > 2.5 times the normal upper limit or alkaline phosphatase > 2.5 times the normal upper limit , unless it is attributed to hepatic infiltration by lymphoma. 12. Pregnant or breast-feeding. 13. Females of childbearing potential who do not agree to undergo pregnancy tests or repeated use effective birth control while included in the clinical trial. 14. Males patients (whose sexual partners are women of childbearing potential ) that not accept use effective birth control methods while included in the clinical trial | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Recurrent Adult Acute Myeloid Leukemia Acute Myeloid Leukemia, in Relapse Male or female patients aged ≥ 18 years Documented definitive diagnosis of AML (according to WHO 2008) that is relapsed/refractory to standard treatment, for which no standard therapy is available or the patient refuses standard therapy WBC count ≤ 10 x 109/L at Visit 1/Day 1; hydroxyurea is allowed to lower WBC count Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Visit1/Day 1 Life expectancy of at least 2 months Adequate renal and hepatic laboratory assessments: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic organ involvement, Total Bilirubin ≤2.0 × ULN, Serum creatinine ≤2.0 × ULN Able to give written informed consent before any study related procedure Acute promyelocytic leukaemia (French-American-British M3 classification) Active central nervous system involvement Haematopoietic stem cell transplantation (HSCT) performed within 3 months prior to Screening Visit Active infection requiring intravenous antibiotics Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety or interfere with the patient's ability to comply with the study activities Anti-tumour therapy within 14 days of study Visit 1/Day 1, excluding hydroxyurea Prior participation in an investigational study (procedure or device) within 21 days of study Visit 1/Day 1 Radiotherapy within 28 days prior to study Visit 1/Day 1 or scheduled along the study conduct Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) Other active malignancies. History of malignancy in the last 12 months (except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast or non-melanoma skin cancer) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-90.0, Osteoarthritis Age between 18 and 90 years Patients with no previous treatment Patients with Knee osteoarthritis grade 1-2 ( Kellgren-Lawrence based on radiographic findings) Age <18 and > 90 years Patients with Knee osteoarthritis grade 3-4 ( Kellgren-Lawrence based on radiographic findings) Patients with asociated Rheumatic syndromes Patients with anticoagulant therapy Patients with hepatic problems, Diabetes Mellitus, Coagulopathy, hearth conditions, immunodepressed, or infections Pregnant patients Patients with prosthetic or orthotic Patients with hemoglobin values < 11g/dl , platelets < 150,000/μL | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, CLL New diagnosed patients with CLL (untreated) Not treated with immunoglobulin Not treated with steroids | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Richter's Transformation Histologically confirmed Richter's transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). 2. Availability of fresh or archived tumor tissue. 3. FDG PET-CT (disease) positive baseline scan with measurable disease. 4. ECOG performance status of 0-1. 5. Evidence of disease progression at study entry. 6. Discontinuation of prior anticancer therapy for ≥ 7 days prior to C1D1 and recovered to ≤ CTCAE grade 2 (or baseline) from any acute or chronic toxicity associated with prior therapy. 7. Must have previously received at least one prior chemotherapeutic regimen for RT Previously untreated RT patients deemed ineligible for, or that refuse, intensive chemotherapy are eligible. 8. Adequate bone marrow, renal, and hepatic function. 9. Normal Coagulation profile. 10. Agreement to use acceptable methods of contraception during the study and for ≥ 120 days after the last dose of PNT2258 if sexually active and able to bear or beget children. 11. Ability to participate in the clinical study for a minimum of at least 2 cycles (6 weeks) Concurrent non-hematologic malignancies requiring treatment. 2. No more than 2 prior regimens for DLBCL. 3. Hodgkin's variant of Richter's lymphoma, accelerated CLL, composite lymphoma, interdigitating dendritic cell sarcoma, sarcoma, EBV-associated lymphoma or prolymphocytic transformation. 4. Ongoing risk of bleeding. 5. CNS or leptomeningeal involvement of lymphoma 6. Concurrent clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram or laboratory finding that, in the opinion of the investigator, could adversely affect the safety of the subject or impair the assessment of the study results. 7. Pregnancy or breast-feeding. 8. Previous exposure to PNT2258 | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Mediastinal Lymphadenopathy adults (18 Years and older) with mediastinal lymphadenopathy known or suspected malignancy no informed consent pts with anterior mediastinal lesions contraindications to EBUS | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Crohn Disease Colitis, Ulcerative Intestinal Helminthiasis The included volunteer is a researcher within parasitology with main focus on Trichuris trichiura and Trichiura suis. He planned to infect himself and contacted our department with the purpose of being monitored during this infection for safety (medical supervision) and research reasons. The only clinical criterion for his in the study was that he was healthy N/A | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Rectal Adenocarcinoma Anal Adenocarcinoma Anal Squamous Cell Carcinoma Subjects with histologically confirmed stage II and III rectal adenocarcinoma or subjects with histologically confirmed stage II and III anal SCC 2. Subjects greater than 18 years of age. 3. Subjects who will undergo prescribed neoadjuvant chemotherapy and/or radiotherapy and have surgical resection prior to further treatment or pathologic confirmation of treatment response using endoscopy or ultrasound. 4. Subjects with twenty (20) unstained sections on charged slides available from tumor block (FFPE) used for the diagnosis of rectal/anal carcinoma or adjacent to this block (pre-neoadjuvant biopsy sample); and four (4) unstained slides available from post-chemoradiation surgery to allow for blinded pathology review and assessment of pathCR, partial CR, or exCTRT. Slides from surgical resection are not necessary in cases with documented post-surgical determination of response by ultrasound or endoscopy. 5. Subjects willing to complete study follow up for outcomes. 6. Subjects from who informed consent can be obtained Subjects with carcinoma in situ or Stage I rectal/anal carcinoma. 2. Subjects with Stage IV rectal/anal carcinoma. 3. Subjects with diagnosis of other malignant tumors with the exception of non-melanoma skin cancers cured by resection only. 4. Subjects that have received prior chest or upper abdomen radiotherapy and/or system chemotherapy within the past 5 years 5. Subjects who are unwilling to complete study follow up 6. Employees and family members of Investigator | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Loss of Chromosome 17p Recurrent Chronic Lymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Small Lymphocytic Lymphoma Richter Syndrome Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL), refractory to or relapsed after at least one prior standard therapy or untreated with deletion (del)(17p) by fluorescence in-situ hybridization (FISH) (high-risk cytogenetics) and have an indication for treatment by IWCLL 2008 (Cohort 1) OR have been on ibrutinib for at least 9 months with measurable persistent disease (absolute lymphocyte count [ALC] > 4 K/muL, any lymph node > 1.5 cm by computed tomography [CT] scan, or > 30% lymphocytes on bone marrow aspirate differential) (Cohort 2), OR patients will have a diagnosis of RT, refractory to and/or relapsed after at least one prior standard therapy or untreated with del(17p) by FISH (high-risk cytogenetics) (Cohort 3) Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Total bilirubin =< 1.5 x upper limit of normal (ULN); for patients with Gilbert's disease, total bilirubin up to =< 3 x ULN is allowed provided normal direct bilirubin Serum creatinine =< 1.5 x ULN Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 23 weeks following the last dose of the study drugs; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy; males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drugs Patients or their legally authorized representative must provide written informed consent History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses); if patients have another malignancy that was treated within the last 2 years, such patients may be enrolled if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center and after consultation with the principal investigator Any major surgery, radiotherapy, cytotoxic chemotherapy, biologic therapy, immunotherapy, immunomodulatory drugs, experimental therapy within 4 weeks prior to the first dose of the study drugs; Note: prior therapy with anti cluster of differentiation (CD)20 monoclonal antibody, anti CD52 monoclonal antibody, and lenalidomide are allowed; for oral targeted therapies (such as idelalisib, venetoclax), a washout of 3 days is allowed Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 2 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification History of stroke or cerebral hemorrhage within 2 month Patients who have uncontrolled hypertension (defined as sustained systolic blood pressure >= 160 mmHg or diastolic >= 100 mmHg) Known evidence of active cerebral/meningeal CLL; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring steroid therapy Patients with autoimmune diseases are excluded: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, Wegener's granulomatosis) Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with active acute or chronic graft-versus host disease are excluded; patients must be off immunosuppression for graft-versus host disease (GVHD) for at least 30 days before cycle 1 day 1 Patients with organ allografts (such as renal transplant) are excluded | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 9.0-17.0, Narrative Exposure Therapy Treatment as Usual 17 years old has spent some part of her/his life living in a country where organized violence was taking place, or at a refugee camp suffers from significant stress symptoms thought be trauma-related acute psychosis intellectual disability | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, B-cell Chronic Lymphocytic Leukemia Has Eastern Cooperative Oncology Group (ECOG) performance status of less than (<) 2 Has a diagnosis of Chronic Lymphocytic Leukemia (CLL) that meets published diagnostic (Hallek 2008): 1. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing at least one B-cell marker (Cluster of Differentiation 19 [CD19], CD20, or CD23) and CD5 2. The diagnosis of CLL requires a history of lymphocytosis with a B-lymphocyte count greater than or equal to (>=) 5,000/microliter (μl) Active disease meeting at least one of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Must have received at least one prior therapy for CLL and not be appropriate for treatment or retreatment with purine analog based therapy Able to receive all outpatient treatment and all laboratorial monitoring at the institution that administers program drug Known central nervous system (CNS) lymphoma or leukemia Known prolymphocytic leukemia or history of or currently suspected Richter's transformation Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) Prior exposure to ibrutinib or randomization in an ibrutinib study Requires treatment with a strong Cytochrome P3A4/5 (that is, CYP3A4/5) Inhibitor | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymphadenopathy Tuberculosis Sarcoidosis Patients with isolated intrathoracic lymphadenopathy Suspicion of primary lung cancer on CT or PET scan Suspicion of pulmonary tuberculosis on CT or PET scan Suspicion of sarcoidosis of lung parenchyma on CT or PET scan | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 1.0-80.0, Portal Vein, Cavernous Transformation Of Hypertension, Portal All patients with portal hypertention who have enough image information to confirm cavernous transformation of portal vein Patients with known severe dysfunction of heart, lung, brain, kidney and other vital organs | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Hypertension, Portal Portal Vein, Cavernous Transformation Of All patients with portal hypertension who have the history of splenectomy and have enough image information to confirm occlusion of portal vein Patients with known severe dysfunction of heart, lung, brain, kidney and other vital organs | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Men and women with histologically confirmed disease as defined by the following CLL: clonal B-lymphocytosis greater than or equal to 5,000 cells/microL SLL: lymphadenopathy with the tissue morphology of CLL but that are not leukemic, < 5,000 cells/microL Immunophenotypic profile or immunohistochemistry read by an expert pathologist as consistent with CLL. This will CD5, CD19, and CD20 expression by the CLL cells typically also with CD23 expression, but CD23 negative cases may be included if there is an absence of t(11;14). 2. Active disease as defined by at least one of the following (IWCLL consensus criteria) Weight loss greater than or equal to 10% within the previous 6 months Extreme fatigue Fevers of greater than 100.5 F for greater than or equal to 2 weeks without evidence of infection Night sweats for more than one month without evidence of infection Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive or progressive splenomegaly Transformed CLL, including Hodgkin and non-Hodgkin lymphoma 2. Active autoimmune hemolytic anemia or thrombocytopenia 3. Known bleeding disorders 4. Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper limit of normal unless due to Gilbert's disease, aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than or equal to 2.5 times institutional upper limit of normal unless due to infiltration of liver, Child-Pugh class B or C 5. Impaired renal function: estimated glomerular filtration rate (GFR) < 30ml/min/1.73m(2) based on CKD-EPI 6. Life-threatening illness, medical condition or organ system dysfunction which, in the investigators opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib and fludarabine, or put the study outcomes at undue risk 7. Concomitant immunomodulatory therapy, chemotherapy, radiotherapy or experimental therapy 8. Active Hepatitis B or Hepatitis C infection 9. HIV infection 10. Female patients who are currently in pregnancy, or unwilling to use acceptable methods of contraception or refrain from pregnancy if of childbearing potential or currently breastfeeding. Male patients who are unwilling to follow the contraception requirements described in this protocol. 11. Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements. 12. Unable to understand the investigational nature of the study or give informed consent. 13. Individuals < 18 years old 14. Known hypersensitivity to any component of ibrutinib or fludarabine 15. Requires concomitant anticoagulation with Coumadin (warfarin) or other vitamin K antagonists. 16. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for greater than or equal to 2 years or which will not limit survival to < 2 years 17. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction 18. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug 19. Major surgery within 4 weeks of first dose of study drug 20. Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification, or a history of myocardial infarction or unstable angina, or acute coronary syndrome within 6 months of screening. 21. Subjects who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitor | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lung Cancer Non-Small Cell Lung Cancer Ability and willingness to provide informed consent 2. Ability and willingness to comply with the requirements of the study protocol 3. Age >/= 18 years. 4. Representative tumor specimens in paraffin blocks (preferred) or at least 10 unstained slides, with an associated pathology report, requested at any time prior to study entry. Only tissue from core needle, punch, or excisional biopsy sample collection will be accepted. Fine-needle aspiration, brushing, and lavage samples are not acceptable. For all biopsy types, submitted blocks should have sufficient tissue to generate at least 10 sections, and tissue for which the pathology report specifies that the overall tumor content is low (e.g., "sparse" or "scant") is not acceptable. 5. Cont'd from #4: If archival tissue is either insufficient or unavailable, the patient will need to consent to and undergo a pre treatment core or excisional biopsy sample collection of the tumor. Fine needle aspiration, brushing, and lavage samples are not acceptable. The immediate unavailability of tissue blocks or unstained slides aside from the slides needed for diagnostic confirmation of lung cancer does not patients from this trial. If the patient chooses to not undergo a repeat biopsy aside from biopsy for diagnostic purposes, the patient will still be eligible to enroll on 2014-0722. However, availability of core or excisional biopsy samples must be ascertained prior to enrollment. 6. Patients must have histologically confirmed, untreated non-small cell lung cancer that are considered non-metastatic, unresectable for which chemoradiation is the definitive therapy. 7. Patients will have the option to enroll on blood collection protocol, LAB09-0983, for serial collections of blood before, during intervals of treatment, and at follow up visits. Enrolling on the LAB09-0983 protocol is not required to enroll on the 2014-0722 study. 8. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1): Absolute neutrophil count (ANC) >/= 1500 cells/uL *White Blood Cells (WBC) counts > 2500/uL *Lymphocyte count >/= 500/uL *Platelet count >/= 100,000/uL; for patients with hematologic malignancies, platelet count >/= 75,000/uL *Hemoglobin >/= 9.0 g/dL *Total bilirubin </= 1.5 x Upper Limit of Normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level </= 3 x ULN may be enrolled. *Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) </= 3.0 x ULN 9. Cont'd from #8: Serum creatinine </= 1.5 x ULN or creatinine clearance >/= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL) 10. Measurable disease per Response Evaluation In Solid Tumors (RECIST) v1.1 11. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 12 months after the last dose of MPDL3280A, and for male patients continued use of contraception must be for a minimum of 3 months post-treatment. 12. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 as long as patients are eligible to receive chemotherapy along with concurrent radiotherapy 13. International Normalized (INR) and aPTT </= 1.5 x ULN * This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose Patients with any distant metastasis (liver, lung, bone, brain). 2. Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed: *Hormone-replacement therapy or oral contraceptives *Herbal therapy > 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1) 3. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease 4. Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma 5. Pregnancy, lactation, or breastfeeding 6. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies 7. Inability to comply with study and follow-up procedures 8. History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis *Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. *Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. *Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: *Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations *Rash must cover less than 10% of body surface area (BSA) 9. Cont'd from #9: *Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) *No acute exacerbations of underlying condition within the last 12 months (not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids) 10. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan 11. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 12. History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic or acute) or hepatitis C infection *Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. *Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for hepatitis C virus ribonucleic acid (HCV RNA). 13. Active tuberculosis 14. Severe infections within 4 weeks prior to Cycle 1, Day 1 including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia 15. Signs or symptoms of severe infection (sepsis) within 2 weeks prior to treatment start. 16. Major surgical procedure within 28 days prior to treatment start or anticipation of need for a major surgical procedure during the course of the study (EBUS and mediastinoscopy and VATS are not considered major surgical procedures). 17. Administration of a live, attenuated vaccine within 4 weeks before treatment start or anticipation that such a live attenuated vaccine will be required during the study *Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to treatment start or at any time during the study. 18. Malignancies within 3 years prior to treatment start, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., CLL Rai Stage 0, prostate cancer with Gleason score </= 6, and PSA </= 10 mg/mL, etc.) 19. ARE Medication-Related *Treatment with systemic immunostimulatory agents (including but not limited to IFN-a, IL-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to the start of chemoradiation.Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half lives of the investigational product, whichever is longer) 20. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1 *Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled. *The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. 21. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 22. Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Anemia Cancer Fatigue Chronic Lymphocytic Leukemia Fever Infectious Disorder Lymphadenopathy Lymphocytosis Night Sweats Prolymphocytic Leukemia Recurrent Chronic Lymphocytic Leukemia Richter Syndrome Secondary Malignant Neoplasm Thrombocytopenia Weight Loss All patients must have a diagnosis of chronic lymphocytic leukemia (CLL) by immunophenotyping and flow cytometry analysis of blood or bone marrow Patients must meet for treatment based on the proposed by National Cancer Institute (NCI)-sponsored CLL Working Group to at least one of the following Weight loss of more than 10% over the preceding 6 months; or Extreme fatigue attributable to progressive disease; or Fever or night sweats without evidence of infection; or Worsening anemia (Rai stage Ill) or thrombocytopenia (Rai stage IV); or Massive lymphadenopathy (> 10 cm) or rapidly progressive lymphocytosis (lymphocyte doubling time < 6 months); or Prolymphocytic or Richter's transformation; or Patients with CLL who have received at least one prior line of therapy; or Patients with CLL who have frequent infections and/or recurrent secondary cancers Receipt of glucocorticoids (with the exception of inhaled glucocorticoid steroids for the use of allergic rhinitis or pulmonary disease) within 2 weeks of registration Autoimmune disease related to CLL, e.g., idiopathic thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, is permitted if not requiring active treatment | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Richter Syndrome Confirmed diagnosis of B-cell Chronic Lymphocytic Leukemia or Richter's Transformation Refractory to or relapsed after at least 1 prior treatment regimen Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Any major surgery, chemotherapy or immunotherapy within the last 14 days Known hepatitis B virus, hepatitis C virus or HIV infection Active autoimmune disorder (with the exception of autoimmune hemolytic anemia or ITP) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 20.0-999.0, Chronic Lymphocytic Leukemia (CLL) Patients with confirmed diagnosis of CLL, either histologically proven or with immunophenotypical pattern by flowcytometry 2. The diagnosis of CLL was made after 2000; the complete medical history and the laboratory data are available for collections. 3. Age of 20 or older 4. Willing to cooperate with the informed consent procedure and the collections of blood samples and medical history. 5. There are no limitations about organ functions, performance status, pregnancy or breast feeding status, or concomitant diseases or medicines. 6. The patient's peripheral hemogram shows apparent leukocytosis (>15 k/μL) with lymphocytosis (lymphocytes+atypical lymphocytes >55%); the data should me within 3 months before study enrollment The patient's past history, including the diagnostic test results, the prior CLL-related treatment courses, the drug history, et.al, is not available. 2. The patient cannot complete the informed consent procedures. 3. The diagnosis is T-CLL, or the patients have been in complete remission without peripheral leukemia cells | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia NPP 1. Patients ≥18 years of age. 2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 3. A minimum of one prior line of systemic chemotherapy, chemo-immunotherapy, or an alemtuzumab-based regimen, consisting of at least two cycles of therapy. 4. Relapsed or refractory CLL with one or more of the following Presence of deletion of the short-arm of chromosome 17 (ie 17p deletion) Relapsed: Failed two or more previous treatments, at least one with a purine analogue such as fludarabine Relapsed: Progression-free interval of less than 24 months from completing treatment with a nucleoside analogue, or bendamustine-containing regimen in combination with an anti-CD20 monoclonal antibody such as rituximab Refractory: Failure to respond to a prior chemotherapy-based treatment, stable disease, or disease progression while on treatment. 5. Patient has active CLL requiring treatment as defined by the IWCLL 2008 criteria. A minimum of one of the following is required Evidence of progressive marrow failure, as manifested by the development of, or worsening of, anemia or thrombocytopenia Massive (at least 6 cm below the left costal margin), progressive, or symptomatic splenomegaly. c. Massive nodes (at least 10 cm in longest diameter), progressive, or symptomatic lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time of less than 6 months (which may be extrapolated). For patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/mL), lymphocyte doubling time should not be used as a single parameter to define indication for treatment. Factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs: i. Unintentional weight loss >10% within the previous 6 months prior to screening. ii. Significant fatigue (inability to work or perform usual activities). iii. Fever higher than 38.0°C for 2 or more weeks without evidence of infection. iv. Night sweats for more than 1 month without evidence of infection. 6. Haematology values within the following parameters Absolute neutrophil count (ANC) of ≥0.75 x109/L independent of growth factor support Previous treatment with ibrutinib or participation to an ibrutinib clinical trial (ibrutinib or comparator arm). 2. Eligible to participate in a currently recruiting ibrutinib clinical trial. 3. Previously received ibrutinib as part of a clinical trial. 4. Previously received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib. 5. Currently enrolled in an interventional clinical trial. 6. Currently receiving chemotherapy, anticancer immunotherapy, or experimental therapy. 7. Currently recovering from acute toxicities of prior treatment for CLL. 8. Received stem cell transplantation within the past 6 months. 9. Evidence of graft-versus-host disease and/or requires immunosuppressant therapy. 10. Major surgery within the past 4 weeks or a major wound that has not fully healed. 11. History of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B. 12. Ongoing uncontrolled active systemic infection. 13. Uncontrolled autoimmune haemolytic anemia (AIHA). 14. Uncontrolled idiopathic thrombocytopenic purpura (ITP). 15. Central nervous system leukemia/lymphoma or Richter's transformation. 16. Diagnosed or treated for another malignancy, other than CLL, except for Malignancy treated with curative intent and with no known active disease present for ≥3 years prior to entering this named patient program and considered to be at low risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated cervical carcinoma in situ without evidence of disease. 17. Stroke within the past 6 months. 18. Intracranial haemorrhage within the past 6 months. 19. Requires anticoagulation with warfarin or equivalent vitamin K antagonist (e.g. phenprocoumon). 20. Requires treatment with a strong CYP3A inhibitor. 21. Clinically significant cardiovascular disease such as Uncontrolled or symptomatic arrhythmias Congestive heart failure Myocardial infarction within the past 6 months Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. 22. Patient has any life-threatening illness, medical condition, clinically significant | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-50.0, Beta-Thalassemia Sickle Cell Disease Provision of written informed consent for this study by subjects, or as applicable, subject's parent(s)/legal guardian(s) Treated with drug product for therapy of a hemoglobinopathy in a bluebird bio-sponsored clinical study Able to comply with study requirements There are no for this study | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-73.0, Lymphoma, B-Cell Lymphoma, Non-hodgkins Malignancy Patients with the following malignancies are potentially eligible: any B-cell lymphoma, and chronic lymphocytic leukemia (CLL). Patients with indolent malignancies that have transformed to diffuse large B-cell lymphoma are eligible Clear CD19 expression must be uniformly detected on 75% or more of malignant cells from either bone marrow or a leukemia or lymphoma mass by flow cytometry or immunohistochemistry. These assays must be performed at the National Institutes of Health. It is preferable but not required that the specimen used for CD19 determination comes from a sample that was obtained after the patient s most recent treatment. If paraffin embedded unstained samples of bone marrow involved with malignancy or a lymphoma mass are available, these can be shipped to the NIH for CD19 staining; otherwise, new biopsies will need to be performed for determination of CD19 expression DLBCL patients must have received at least two prior chemotherapy-containing regimens at least one of which must have contained doxorubicin and a monoclonal antibody. Follicular lymphoma patients must have received at least 2 prior regimens including at least 1 regimen with chemotherapy. All other lymphoma and leukemia patients must have had at least 1 prior chemotherapy-containing regimen. All patients with CLL or small lymphocytic lymphoma must have had prior treatment with ibrutinib or another signal transduction inhibitor Patients must have measurable malignancy as defined by at least one of the below Lymphoma or leukemia masses that are measurable (minimum 1.5 cm in largest diameter) by CT scan is required for all diagnoses except CLL. All masses must be less than 10 cm in the largest diameter For a lymphoma mass to count as measurable malignancy, it must have abnormally increased metabolic activity when assessed by positron emission tomography (PET) scan For CLL and lymphoma with only bone marrow involvement no mass is necessary, but if a mass is not present, bone marrow malignancy must be detectable by flow cytometry in lymphoma and CLL Other Greater than or equal to 18 years of age and less than or equal to age 73 Patients that require urgent therapy due to tumor mass effects or spinal cord compression Patients that have active hemolytic anemia Patients with second malignancies in addition to their B-cell malignancy are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 4 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant Active uncontrolled systemic infections (defined as infections causing fevers and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours), active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, history of ventricular tachycardia or ventricular fibrillation, active cardiac arrhythmias (active atrial fibrillation is not allowed, resolved atrial fibrillation not requiring current treatment is allowed (anticoagulants count as current treatment) ), active obstructive or restrictive pulmonary disease, active autoimmune diseases such as rheumatoid arthritis Patients will not be seen for screening appointments or enrolled on the protocol if they have been hospitalized within the 7 days prior to the screening appointment or the date of protocol enrollment Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) Systemic corticosteroid steroid therapy of any dose is not allowed within 14 days prior to the required leukapheresis, or the initiation of the conditioning chemotherapy regimen. Corticosteroid creams, ointments, and eye drops are allowed History of severe immediate hypersensitivity reaction to any of the agents used in this study Patients with current CNS involvement by malignancy (either by imaging or cerebrospinal fluid involvement or biopsy-proven) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Multiple Myeloma Subjects must satisfy the following to be enrolled into the study: 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF) 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements 4. Subject must have documented diagnosis with previously untreated (for cohort C, the induction and consolidation treatment along with the first autologous stem cell transplantation (ASCT) are allowed), symptomatic multiple myeloma (MM) as defined by the below: MM diagnostic (all 3 required) Monoclonal protein present in the serum and/or urine Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma Any one or more of the following myeloma defining events: 1. one or more of the following Myeloma-related organ dysfunction (at least one of the following) (C) Calcium elevation (serum calcium >11.5 mg/dl )(>2.65 mmol/L) (R) Renal insufficiency (serum creatinine >2 mg/dl)(177 µmol/L or more) or creatinine clearance < 40 ml/min (A) Anemia (hemoglobin <10 g/dL or >2 g/dL below the lower limit of laboratory normal) (B) Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-computed tomography (PET-CT) 2. one or more of the following biomarkers of malignancy Clonal bone marrow plasma cell percentage ≥60% Abnormal serum free light-chain ratio ≥100 (involved kappa) or < 0.01 (involved lambda) The presence of any of the following will a subject from enrollment: 1. Previous treatment with anti-myeloma therapy (does not radiotherapy, bisphosphonates, or a single short course of steroid (ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of Cycle 1 Day 1), for Cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed) 2. Any of the following laboratory abnormalities: 1. Absolute neutrophil count (ANC) < 1,000/μL 2. Untransfused platelet count < 75,000 cells/μL 3. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (SGOT/AST) or alanine aminotransferase (SGPT/ALT) > 2.5*upper limit of normal (ULN) 4. Serum total bilirubin > 1.5*ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome 5. Corrected serum calcium >13.5 mg/dL (> 3.4 mmol/L) 3. Renal failure requiring hemodialysis or peritoneal dialysis 4. Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, subject with unstable cardiac disease as defined by: cardiac events such as myocardial infarction (MI) within the past 6 months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment 5. Peripheral neuropathy ≥ Grade 2 6. Primary AL (immunoglobulin light-chain) amyloidosis and myeloma complicated by amyloidosis 7. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following non-invasive malignancies: 1. Basal cell carcinoma of the skin 2. Squamous cell carcinoma of the skin 3. Carcinoma in situ of the cervix 4. Carcinoma in situ of the breast 5. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative 8. Subjects is positive for human immunodeficiency virus (HIV); chronic or active hepatitis B or active hepatitis A, or C 9. Subject had prior exposure to immunotherapy, including, but not limited to, other anti CTLA-4,anti-PD-1, anti-PD-L1 monoclonal antibody or inhibitor, cell-based therapies, or cancer vaccines 10. Subjects has history of organ or allogeneic stem cell transplantation 11. Subjects who have had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma, or plasma cell leukemia 12. Known or suspected hypersensitivity to the excipients contained in the formulation of durvalumab, lenalidomide, or dexamethasone 13. Major surgery (as defined by the investigator) within the 28 days prior to the first dose of study treatment 14. Received prior treatment (for any reason)with a monoclonal antibody within 5 half-lives of initiating study treatment 15. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment 16. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion: 1. Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection); 2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent; 3. Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication); 17. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (eg, colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis); myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: 1. Subjects with vitiligo or alopecia; 2. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; or 3. Subjects with psoriasis not requiring systemic treatment; 18. History of primary immunodeficiency 19. Subject has incidence of gastrointestinal disease that may significantly alter the absorption of LEN 20. Receipt of live, attenuated vaccine within 30 days prior to the first dose of durvalumab 21. Unable or unwilling to undergo protocol required thromboembolism prophylaxis(for Cohort C, this will be only for the subjects who have a history of VTE) 22. Females who are pregnant, nursing or breastfeeding, or intend to become pregnant during the participation to the study 23. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 24. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study 25. Any condition that confounds the ability to interpret data from the study | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Mediastinal Lymphadenopathy Non-small Cell Lung Carcinoma Sarcoidosis ≥18 years of age Suspected or tissue proven sarcoidosis (stage I or II based on CT/PET-CT) and referred for diagnostic endosonographic work up or Suspected or tissue proven NSCLC with suspected mediastinal lymph nodes within reach of EUS-FNA Inability and willingness to provide informed consent Inability to comply with the study protocol Patients with known allergy for fluorescein use of betablokker within 24 hours before procedure possible pregnancy or lactating women | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Cold Agglutinin Disease Autoimmune Hemolytic Anemia CAD diagnosis defined by the combination of - 1. Chronic hemolysis 2. Cold agglutinin titer 64 or higher 3. Positive direct antiglobulin test when performed with polyspecific antiserum, negative (or only weakly positive) with anti-IgG, and strongly positive with anti-C3d 2. The presence of a clonal B-cell lymphoproliferative disorder defined by - 1. Monoclonal band by serum electrophoresis with immunofixation, and/or 2. CD20 positive lymphocyte population with cellular kappa/lamda-ratio higher than 3.5 or less than 0.9, using flowcytometric immunophenotyping of bone marrow aspirates 3. Indication for therapy, i.e. significant anemia and/or considerable cold-induced circulatory symptoms 4. Written informed consent An aggressive lymphoma 2. Non-lymphatic malignant disease other than basal cell carcinoma of the skin. A history of probably cured cancer is not an criterion. 3. Known HIV infection 4. Acute or chronic hepatitis B or C 5. Liver failure or active parenchymal liver disease. Bilirubin levels higher than 51 mol/L (3.0 mg/dL) when due to hepatic impairment. Elevated serum bilirubin level due to hemolysis is not an criterion. 6. Pregnancy or breast-feeding 7. Patients of childbearing age who are not willing to use safe contraception during the entire study period and 6 months following its cessation 8. All contraindications to the study drugs will be regarded as 9. Age below 18 years 10. Inability to cooperate | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Mediastinum Age 18 years and Older Predominant Subcarinal or Lower Left paratracheal located mediastinal lymphadenopathy/mediastinal lesions at least >1cm in Short axis diameter Patients who give consent Refusal of consent for the procedure Any contraindications to Bronchoscopy / Endobronchial Ultrasound Pregnancy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Cancer of the Lung Lung Cancer Lung Neoplasms Adenocarcinoma of the Lung Non Small Cell Carcinoma of the Lung Small Cell Carcinoma of the Lung years of age or older, not previously diagnosed with cancer (except for basal cell carcinomas of the skin or a diagnosis of cancer within a month of surgery and for which the surgical procedure is being performed) Prior history of cancer | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Arthroscopic Knee Surgery Lower Limb Fractures Back Pain and Asymmetric Gait Complex Regional Pain Syndrome days to 1 month following arthroscopic knee surgery(n=10) Following fractures in lower limb with pain during weight-bearing (n=10) Back pain and asymmetrical gait (n=10) Complex Regional Pain Syndrome with pain during weight-bearing (n=10) Neurological condition that does not permit walking on soft surface (drop foot) Wounds on feet | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-90.0, Leukemia, Lymphocytic, Chronic, B-Cell patients fulfilling clinical and immune-phenotypic for CLL none | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-90.0, Leukemia, Lymphocytic, Chronic, B-Cell patients with CLL | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-99.0, Leukemia, Lymphocytic, Chronic, B-Cell Diagnosis of Chronic Lymphocytic Leukemia (CLL) established according to International Workshop Chronic Lymphocytic Leukemia (IWCLL) criteria Relapsed or refractory CLL pre-treated with at least one prior line of systemic therapy for CLL Indication for treatment consistent with IWCLL i.e. at least one of the following should be met Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive or progressive or symptomatic splenomegaly Massive nodes or progressive or symptomatic lymphadenopathy Progressive lymphocytosis in the absence of infection, with an increase in blood Absolute Lymphocyte Count (ALC) >=50% over a 2-month period, or a lymphocyte doubling time (LDT) of <6 months (as long as initial ALC was >=30000/µl) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs unintentional weight loss of 10% or more within the previous 6 months Known transformation of Chronic Lymphocytic Leukemia (CLL) to an aggressive B-cell malignancy at the time of screening Prior allogeneic stem cell transplant within one year or active graft vs. host disease History of a non-CLL malignancy except for adequately treated in situ, stage 1 or 2 carcinoma in Complete Response (CR), or any other cancer that has been in CR for >=2 years after end of cancer treatment Active, uncontrolled autoimmune cytopenia. Patients with autoimmune cytopenia which is controlled with corticosteroids at doses of <=20 mg prednisolone or equivalent may be enrolled Previous CLL treatment with a CD37-targeting antibody or a CD37-antibody drug conjugate Previous treatment with ibrutinib Previous treatment with another Bruton's Tyrosine Kinase (BTK) -inhibitor Ongoing systemic immunosuppressive therapy other than corticosteroids Active bacterial, viral, or fungal infection requiring systemic treatment at the time of study entry Human Immunodeficiency Virus (HIV) infection | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Prostate Cancer men in the Västra Götaland healthcare region diagnosed with prostate cancer of intermediate risk-level (T1-T2, Gleason score <8 and PSA<20) scheduled for radical prostatectomy ongoing hormonal treatment other difficult physical or psychological conditions diminished cognitive function allergy to soy having taken dietary supplements regularly (daily) during the preceding three months does not understand written Swedish | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Hepatic Cirrhosis At the risk of gastroesophageal variceal hemorrhage; Acute gastroesophageal variceal hemorrhage;Haematemesis and/or melena result in gastroesophageal variceal haemorrhage of liver cirrhosis in the past Splenomegaly or hypersplenism acting as thrombocytopenia (PLT < 75000 cells/mm^3) Consent form must be signed by patients or their guardians before entering the test History of liver surgery or spleen surgery and liver cancer Existence of gastrointestinal endoscopic therapy contraindication;Hemorrhagic shock has not be corrected;Hepatic encephalopathy Sinus bradycardia, bronchial asthma, chronic obstructive pulmonary disease, heart failure, low blood pressure, atrioventricular block, insulin dependent diabetes, peripheral vascular disease, liver function Child Pugh class C Pregnant women and nursing mothers | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, CLL CLL patients intended to receive treatment in 30 days from recruitment to the study CLL patient not about to receive treatment in 30 day of recruitment to the study | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Non-Small-Cell Lung Cancer ≥19 years of age 2. Patients with a primary diagnosis of NSCLC within the past 5 years who are eligible for their first systemic therapy based on disease characteristics. Systemic therapy may any cytotoxic, targeted, immune-based, or otherwise non-local treatment modality. Specific allowed settings the following: 1. Incident metastatic disease (stage IV) undergoing palliative therapy 2. Non-metastatic disease undergoing adjuvant, neoadjuvant, or concurrent chemoradiation with either curative or palliative intent 3. Recurrent or subsequently metastatic disease (any stage) 3. Pathologic confirmation of malignancy prior to initiation of first systemic therapy 4. Submission of archival biospecimen sample(s) (collected up to two years prior) for analysis 5. Availability of key variables at the time of screening (e.g. stage, demographics) 6. Have been fully informed and are able to provide written consent for longitudinal follow-up and agree to be accessible by phone 7. Patients may be concurrently enrolled in unblinded clinical trials, but not blinded clinical trials in which the treatment being administered is unknown Pre-specified enrollment caps have been met (Figure 1) 2. Suspected recurrent or subsequently metastatic disease that is not biopsy confirmed prior to receipt of initial systemic therapy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, CLL SLL HCL Richter´s Transformation Leukemia, Prolymphocytic, B-Cell Leukemia, Prolymphocytic, T-Cell T-LGL Leukemia NK-LGL Leukemia (all must apply) 1. Confirmed diagnosis of CLL, B-PLL, T-PLL, SLL, T or NK-LGL, HCL or Richter's transformation 2. 18 years of age or older 3. Signed, written informed consent 4. Presence of one or more of the following disease situations Newly diagnosed patients without treatment indication (eligible for watch and wait Approach Treatment within a clinical trial according to the AMG or status post participation in a clinical Trial) Treatment with standard therapies approved for the eligible entities or status post treatment (outside of clinical trials) Referral for evaluation the indication for HSCT Relapsed disease status (even if first diagnosis was prior to activation of the registry) Patients without confirmed diagnosis of CLL, B-PLL, T-PLL, SLL, T or NK LGL, HCL or Richter's transformation 2. Cerebral dysfunction, legal incapacity | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Cancer Patient with a histologically proven cancer regardless of the location (solid tumor or not) except brain tumor 2. Patient should receive chemotherapy (any indication) associated with overall risk of neutropenia greater than or equal to 20% 3. Age ≥ 18 years 4. Performance Status ≤ 3 5. Patient with Internet access and an email box 6. Patient affiliated to a social security scheme 7. Patient has given its written consent before any specific procedure for the study Symptomatic brain metastases 2. Persons deprived of liberty, under guardianship or under curators 3. dementia, mental impairment or psychiatric illness that may affect the patient's informed consent and / or protocol adherence and monitoring of the test 4. Patient unable to submit the protocol followed for psychological, social, family or geographical reasons 5. Pregnant or breastfeeding 6. Patients at risk of severe neutropenia (Absolute Neutrophils Count <0.1 Giga / L within 7 days prior to acute leukemia, auto or allograft) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-95.0, Leukemia, Lymphocytic, Chronic, B-Cell Diagnosis of chronic lymphatic leukemia Score of Matutes <4 | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 1.0-31.0, B Acute Lymphoblastic Leukemia Central Nervous System Leukemia Ph-Like Acute Lymphoblastic Leukemia Testicular Leukemia Patients must be enrolled on APEC14B1 and consented to Screening on the Part A consent form prior to enrollment on AALL1131 White Blood Cell Count (WBC) Age 1-9.99 years: WBC >= 50 000/uL Age 10-30.99 years: Any WBC Age 1-30.99 years: Any WBC with Testicular leukemia CNS leukemia (CNS3) Steroid pretreatment Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131 With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131 Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction DS HR B-ALL patients with Induction failure or BCR-ABL1 Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs Lactating females are not eligible unless they have agreed not to breastfeed their infant Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Haemodialysis >18 patient under haemodialysis treatment patient not objecting to study Patient with known cardiac arrythmias | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 19.0-999.0, Leukemia, Lymphocytic, Chronic, B-Cell Diagnosis of CLL meeting published diagnostic criteria. 2. CLL currently being treated with Ibrutinib due to relapsed/refractory disease or primary del17p cytogenetic lesions at a daily dose of 420 mg and failure of plasma b2M levels to decrease below 2.5 mg/L after 6 months after starting Ibrutinib persistent lymphocytosis (>5x106 cells/L) and splenomegaly or lymphadenopathy (marker node >1.5 cm on CT scans) after 1 year of taking Ibrutinib. 3. Not currently treated with other agents for CLL. 4. Serum bilirubin, and alanine transferase less than or equal to twice the upper limit of normal. 5. Platelets >75x109/L. Absolute neutrophil count (ANC)>.75x109/L. Hemoglobin greater than or equal to 65 g/L 6. Age >18 years old 7. Eastern Cooperative Oncology Group (ECOG) < 2 Patients with inadequate bone marrow reserve at baseline visit as demonstrated by at least one of the following: a. ANC<.75x109/L b. platelets <75x109/L without the assistance of growth factors, thrombopoietic factors, or platelet transfusions. C. hemoglobin <65 g/L despite transfusions. 2. Patients who have or have had progressive multifocal leukoencephalopathy (PML). 3. Patients with clinically significant bacterial, fungal, parasitic or viral infection, which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 4. Patients with known active hepatitis A, B, C or who are HIV-positive or who are at risk for hepatitis B virus (HBV) reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care prior to alloSCT that confirm a subject is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment. 5. Primary immunodeficiency such as X-linked agammaglobulinemia or common variable immunodeficiency. 6. Patients with active and inactive ('latent') tuberculosis infection. 7. Involvement of the central nervous system by lymphoma or leukemia. 8. Richter's transformation or prolymphocytic leukemia. 9. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura. 10. Use of glucocorticoids above the equivalent of 10 mg of prednisone daily within 4 weeks prior to treatment. 11. Major surgery within 4 weeks prior to treatment. 12. Patients with a history of malignancy in the past 3 years except for treated, early-stage squamous or basal cell carcinoma. 13. History or current diagnosis of uncontrolled or significant cardiac disease, including any of the following: a. myocardial infarction within last 6 months. b. uncontrolled congestive heart failure. c. unstable angina within last 6 months. d. exertional angina. e. clinically significant (symptomatic) cardiac arrhythmias (eg. bradyarrhythmias, sustained ventricular tachycardia, and clinically significant second or third degree block without a pacemaker). 14. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 15. Renal failure requiring dialysis or serum creatinine >176.8 microM and patients with moderate (creatinine clearance of 30-50 ml/min) and severe (creatinine clearance<30 ml/min) renal impairment with platelet counts less than 100,000/ml. 16. Patients with mild, moderate, or severe hepatic impairment or inadequate liver function defined by any of direct bilirubin, alanine amino transferase (ALT), or aspartate aminotransferase (AST)>2.5 x upper limit of normal (ULN). 17. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 18. Patients with known hypersensitivity to ruxolitinib or other JAK1/2 inhibitors, or to their excipients. 19. Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening or 5 half-lives (whichever is longer) prior to the first dose of study drug. 20. Significant concurrent, uncontrolled medical condition which, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol. 21. Subjects who are unable to comprehend or are unwilling to sign an informed consent form (ICF). 22. Sexually active males who do not agree to use condoms during intercourse while taking ruxolitinib and for 3 months after stopping treatment (N.B. the mean elimination half-life of ruxolitinib is around 3 hours) and not father a child in this period. Vasectomized men must also agree to use a condom during intercourse to prevent delivery of ruxolitinib via seminal fluid. 23. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human choriogonadotropin (HCG) laboratory test (>5 mIU/ml). 24. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study duration inclusive of 30 day safety follow up. Highly effective contraception methods Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. Incase of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to screening). the vasectomized male partner should be the sole partner for that subject Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. 25. Use of strong CYP3A4 inhibitors for patients in the phase I component of the trial | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Gastric Adenocarcinoma Esophageal Squamous Cell Carcinoma Nasopharyngeal Carcinoma Head and Neck Squamous Cell Carcinoma "Inclusion Subjects may be entered in the study only if they meet all of the following 1. Fully understand the study and signed the Informed Consent Form (ICF) voluntarily; 2. Subjects with histologically and/or cytologically confirmed advanced and/or metastatic gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma, who meet the following conditions (not applicable to cohort 5, 6, 7, and 8): Subjects with gastric adenocarcinoma must have received at least one line of anti-tumor treatment for advanced gastric adenocarcinoma and have documented tumor progression or be intolerable to the current available chemotherapy regimen. Subjects who have recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant chemotherapy of radical operation are eligible to this study; Subjects with esophageal squamous cell carcinoma must have received at least one line of treatment for advanced esophageal squamous cell carcinoma (including but not limited to anticancer drug treatment or radio-chemotherapy) and have documented tumor progression or be intolerable to the current chemotherapy regimen. Subjects who have recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant therapy (including but not limited to chemotherapy or radio-chemotherapy) of radical operation are eligible to this study; Subjects with nasopharyngeal carcinoma or head and neck squamous cell carcinoma who have received at least one line of treatment for advanced nasopharyngeal carcinoma or head and neck squamous cell carcinoma (including but not limited to anticancer drug treatment or radio-chemotherapy) and have documented tumor progression or be intolerable to other current chemotherapy regimens. Subjects with recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant radio-chemotherapy of radical operation are eligible to this study (only applies for Version 4.1 and the previous ones); while for the working protocol version 5.0, subjects with nasopharyngeal carcinoma can be enrolled only if they meet the following subjects having received at least two lines of treatment for advanced nasopharyngeal carcinoma (including but not limited to anticancer drug treatment and radio-chemotherapy), who are confirmed to have tumor progression or be intolerable to other current chemotherapy regimens; adjuvant or neoadjuvant radio-chemotherapy after radical surgery can be considered as one line of treatment if tumor recurrence or metastasis occurred within 6 months after the end of the radio-chemotherapy. 3. At least one measurable lesion (according to 1.1); Note: Any lesion which received radiotherapy treatment previously cannot be regarded as a target lesion, unless that it has definitely progressed after radiotherapy. 4. Agree to provide archived tumor tissue specimens or have biopsy to collect tumor tissues for PD-L1 IHC measurement in the central laboratory; 5. Males or females aged between 18 and 75 years old; 6. ECOG score of 0-1; 7. Life expectancy ≥ 3 months; 8. The results of laboratory tests performed within 7 days prior to enrollment must meet the following 1. Neutrophils ≥ 1.5×109/L (not applicable to cohort 5, 6, 7, and 8); 2. Platelets ≥ 75×109/L (not applicable to cohort 5, 6, 7, and 8); 3. Hemoglobin ≥ 90 g/L (without receiving infusion of concentrated red blood cells within 2 weeks); 4. Serum creatinine ≤ 1.5× upper limit of normal (ULN), or creatinine clearance > 50 mL/min (not applicable to cohort 5, 6, 7, and 8); 5. Serum total bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3×ULN are acceptable for subjects with Gilbert syndrome); 6. Both AST and ALT ≤ 2.5×ULN; ALT and AST ≤ 5×ULN are acceptable for subjects with liver metastasis; 9. Serum pregnancy test result must be confirmed as negative for women of childbearing potential within 28 days prior to enrollment and the subjects must agree to take effective contraception measures throughout the study treatment period until 60 days after the end of study treatment. Women of childbearing potential are defined as women with sexual maturity, who meet any of the following conditions: 1) no hysterectomy or bilateral oophorectomy; 2) without natural menopause for a consecutive 24 months (patients with menopause after cancer treatment may also have childbearing potential) (i.e. menstruation occurred at any time during the previous consecutive 24 months) (not applicable to cohort 5, 6, 7, and 8). Female partners of childbearing potential of the male subjects should also follow the contraception requirements. Other special for cohort 5, 6, 7, and 8. 1. Subjects with histologically and/or cytologically confirmed advanced and/or metastatic gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma, who meet any of the following conditions: 1. Subjects who have not received any systematic treatment. 2. Subjects who have received any neoadjuvant chemotherapy, adjuvant chemotherapy for the purpose of curing must experience a period for at least 6 months from the end of the last chemotherapy to tumor progression. 3. Subjects with head and neck squamous cell carcinoma must have received radiotherapy for the purpose of curing, and the period from the end of radiotherapy to tumor progression must be at least 1 year. 4. For subjects with gastric carcinoma, Her2 negative is required. HER2 positive is defined as IHC 3+ or IHC 2+ combined with ISH+, and ISH positive is defined as the ratio of the number of HER2 gene copies to the number of CEP17 signals ≥ 2.0. 2. Results of laboratory test conducted within 7 days before enrollment must meet the following 1. Neutrophils ≥ 2×109/L; WBC count ≥ 4×109L and < 15×109/L 2. Platelets ≥ 100×109/L; 3. Hemoglobin ≥ 90 g/L (no infusion of concentrated red blood cells within 2 weeks); 4. Creatinine clearance rate > 60 mL/min, based on the predicted value of Cockcroft-Gault glomerular filtration rate: (140 age) × (weight, kg) × (0.85, if females) 72× (serum creatinine, mg/dL) Or: (140 age) × (weight, kg) × (0.85, if females) 0.818 × (serum creatinine, μmol/L) 5. Serum total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 3 × ULN are acceptable for subjects with Gilbert syndrome); 6. INR and aPTT ≤ 1.5 × ULN, applies only to subjects who have not received anticoagulation; and for subjects who are receiving anticoagulation, the dose for anticoagulation must be stable. 3. Serum pregnancy test result must be confirmed as negative for women of childbearing potential within 28 days prior to enrollment and the subjects must agree to take effective contraception measures throughout the study treatment period until 6 months after the end of chemotherapy or 60 days after the end of study treatment (whichever comes last). Women of childbearing potential are defined as women with sexual maturities, who meet any of the following conditions: 1) no hysterectomy or bilateral oophorectomy; 2) without natural menopause for a consecutive 24 months (patients with menopause after cancer treatment may also have childbearing potential) (i.e. menstruation occurred at any time during the previous consecutive 24 months) . Female partners of childbearing potential of the male subjects should also follow the contraception requirements. Subjects fulfilling any of the following conditions cannot be enrolled in the study: 1. Known hypersensitivity to citric acid monohydrate, dihydrate sodium citrate, mannitol or polysorbate (components of the investigational drug); 2. Anti-tumor treatment with cytotoxic drugs, biological drugs (e.g. monoclonal antibody), immunotherapy (e.g. interleukin 2 or interferon), or other investigational drugs within 4 weeks prior to enrollment; 3. Tyrosine kinase inhibitor treatment within 2 weeks prior to enrollment; 4. Radiotherapy within 4 weeks prior to enrollment, or radioactive drugs within 8 weeks prior to enrollment. However, patients receiving local palliative radiotherapy for bone metastasis lesions can be included; 5. Subjects with any major surgical operation within 4 weeks prior to enrollment or who have not completely recovered from the prior operation (for the definition of major surgical operation, please refer to the Level 3 and Level 4 operations stipulated in the Management of Clinical Application of Medical Technology enforced on May 1, 2009); 6. Toxicity due to any previous anticancer treatment has not recovered to CTCAE Grade 0-1, excluding the following conditions: 1. Alopecia; 2. Pigmentation; 3. Peripheral nerve toxicity recovered to < CTCAE Grade 2 (not applicable to cohort 5, 6, 7, and 8, subjects are not eligible if peripheral neurotoxicity does not restore to normal); 4. Long-term toxicity related to radiotherapy, which will not fully recover as judged by the investigator. 7. Central nervous system metastasis with clinical symptoms (e.g. brain edema, hormone intervention required, or progression of brain metastasis) and/or carcinomatous meningitis. Subjects with prior treatment for brain or meningeal metastasis can be included if they have remained stable clinically for at least 2 months and systemic hormone treatment (Prednisone at a dose of > 10 mg/day or other equivalent hormone formulations) has been discontinued for more than 4 weeks; 8. Subjects with nasopharyngeal carcinoma or head and neck squamous cell carcinoma, who are found to have necrotic lesions by examination within 4 weeks prior to enrollment, for which there is a potential risk of massive hemorrhage as judged by the investigator; 9. Previous or other concurrent malignant tumors (expect for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervix carcinoma in situ, and other malignant tumors which were effectively controlled without treatment over the past 5 years); 10. Any active autoimmune disease or history of any autoimmune disease (including but are not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism or hypothyroidism. Patients with vitiligo or asthma (in childhood) which was completely resolved and without need of any intervention in adulthood can be included. However, subjects with asthma which needs bronchodilator for medical intervention cannot be included); 11. Previous treatments with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody which acts on T-cell co-stimulatory or checkpoint pathway); 12. Subjects diagnosed with active tuberculosis (TB), who are receiving anti-tuberculosis therapy or used to have anti-tuberculosis therapy within 1 year prior to screening; 13. Concomitant diseases requiring long-term treatment with immunosuppressive drugs, or corticosteroids at an effective immunosuppressive dose (Prednisone at a dose of > 10 mg/day or other equivalent hormone formulations) for systemic or local treatment purpose; 14. Subjects who have received any anti-infection vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment; 15. Pregnant or lactating women 16. Positive test for HIV; 17. Positive test for HBsAg, with HBV DNA copies detected as positive (quantitative measurements ≥ 1000 cps/mL); 18. Positive test for chronic Hepatitis C in blood screening test (HCV antibody positive); Any other clinical significant disease or condition, which as evaluated by the investigator, may affect the protocol compliance, signing of inform consent form (ICF), or not suitable to participate into this clinical trial | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, B-cell Non-Hodgkins Lymphoma Chronic Lymphocytic Leukemia Able to provide written informed consent Diagnosis of either Non-CLL B cell malignancy or CLL/SLL Ineligible for or have exhausted standard therapeutic options and have relapsed or refractory disease ECOG performance status 0-2 Fertile patients must agree to use highly effective contraception during and for 4 weeks after last dose of XmAb13676 Able and willing to complete the entire study Additional Patient for the DLBCL Cohort (Expansion Phase) 1. Histologically confirmed diagnosis (specified by 2016 World Health Organization) of DLBCL or transformed low-grade lymphoma with measurable disease 2. Patient must be refractory or have relapsed after 2 or more standard therapeutic options, at least one of which must have included anti-CD20 antibody therapy. 3. Not a candidate for or refusing treatment with hematopoietic stem cell transplantation Additional Patient for the Follicular Lymphoma Cohort (Expansion Phase) 1. Diagnosis of follicular lymphoma Grades 1-3a 2. Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens. Additional Patient for the Mantle Cell Lymphoma Cohort (Expansion Phase) 1. Diagnosis of mantle cell lymphoma 2. Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens. Additional Patient for the Waldenström Macroglobulinemia Cohort (Expansion Phase) 1. Diagnosis of Waldenström macroglobulinemia 2. Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens. Additional Patient for Richter Transformation Cohort (Expansion Phase) 1. Diagnosis of Richter transformation Additional Patient for Other Indolent Lymphomas Cohort (Expansion Phase) 1. Diagnosis of other indolent B-cell, non-Hodgkin's lymphomas, specifically the following: MALT lymphoma, nodal marginal zone lymphoma, and splenic marginal zone lymphoma (NOTE: SLL is not eligible) 2. Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens Cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-CD20 antibodies within 4 weeks, or small molecule or investigational agents within 6 elimination half-lives of the first dose of XmAb13676 Prior allogeneic stem cell or solid organ transplantation Failure to recover from Grade 3 or 4 toxicity from previous treatment Multiple myeloma/plasma cell leukemia or B cell acute lymphoblastic leukemia Known intolerance to CD20 monoclonal antibody therapy History of primary central nervous system lymphoma or neoplastic central nervous system disease Platelet count < 50 x 10^9/L Absolute neutrophil count < 1.0 x 10^9/L Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at screening > 3x upper limit of normal (ULN) Bilirubin > 1.5 mg/dL unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Endobronchial Transbronchial Needle Aspiration Lung Cancer Procore mediastinal lymphadenopathy >10 millimeters lung cancer suspected coagulopathy contraindication for midazolam contraindication for bronchoscopy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Anemia Fatigue Fever Lymphadenopathy Lymphocytosis Night Sweats Recurrent Chronic Lymphocytic Leukemia Recurrent Plasma Cell Myeloma Refractory Chronic Lymphocytic Leukemia Refractory Plasma Cell Myeloma Splenomegaly Thrombocytopenia Weight Loss All subjects must have the ability to understand and the willingness to sign a written informed consent Life expectancy of > 3 months Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 FOR WITH (MM) Diagnosis of multiple myeloma Patients with MM must have measurable disease, defined as one or more of the following Serum M-protein >= 0.5 g/dL Urine M-protein >= 200 mg/24 hr Serum immunoglobulin free light chain (FLC) >= 100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa to lambda FLC ratio IgA patients must have serum quantitative immunoglobulin >= 750 mg/dL Patients with oligosecretory or non-secretory disease must have a documented abnormal free light chain ratio (normal value 0.26 to 1.65) or a value beyond the laboratory calculation range Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period Use of a protease inhibitor for any indication within three months prior to start of study treatment Current or planned use of prohibited meds Liver disease, except Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment Current pancreatitis History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to metformin, ritonavir or any of their ingredients Non-hematologic malignancy within the past 3 years aside from the following exceptions Adequately treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix Prostate cancer < Gleason grade 6 with a stable prostate-specific antigen test (PSA) | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymphadenopathy Indication for EBUS-TBNA Patient has provided written informed consent | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Documented CLL requiring treatment according to iwCLL 2. Age at least 18 years 3. Life expectancy ≥ 6 months 4. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements 5. Adequate bone marrow function indicated by a platelet count >30 x10^9/l (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy) 6. Creatinine clearance ≥70ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 age) x bodyweight) / (72 x creatinine), for women x 0, 85). For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 70 ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min 7. Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome 8. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 12 months after last treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration 9. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2 Any prior CLL-specific therapies (except corticosteroid treatment administere due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents of 20 mg prednisolone are permitted). 2. Transformation of CLL (Richter transformation) 3. Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of three more concurrent treatments being administered for hemolysis 4. Detected del(17p) or TP53 mutation 5. Patients with a history of PML 6. Any comorbidity or organ system impairment rated with a single CIRS (cumulative illness rating scale) score of 4 (excluding the eyes/ears/nose/throat/larynx organ system), a total CIRS score of more than 6 or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could comprise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract) 7. Urinary outflow obstruction 8. Malignancies other than CLL currently requiring systemic therapies, not being treated in curative intention before (unless the malignant disease is in a stable remission due to the discretion of the treating physician) or showing signs of progression after curative treatment 9. Uncontrolled or active infection 10. Patients with known infection with human immunodeficiency virus (HIV) 11. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers 12. Anticoagulant therapy with warfarin or phenoprocoumon, (rotation to alternative anticoagulation is allowed, but note that patients being treated with NOAKs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib) 13. History of stroke or intracranial hemorrhage within 6 months prior to registration 14. Use of investigational agents which might interfere with the study drug within 28 days prior to registration 15. Vaccination with live vaccines 28 days prior to registration 16. Major surgery less than 30 days before start of treatment 17. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products 18. Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial 19. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly) 20. Fertile men or women of childbearing potential unless: 1. surgically sterile or ≥ 2 years after the onset of menopause 2. willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment 21. Legal incapacity 22. Prisoners or subjects who are institutionalized by regulatory or court order 23. Persons who are in dependence to the sponsor or an investigator | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL) Participant must have a diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL)/SLL that meets 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) NCI-WG Guidelines and the following Participant must have an indication for treatment according to the 2008 Modified iwCLL National Cancer Institute-Working Group (NCI-WG) Guidelines CLL participant must have measurable disease (B-lymphocytosis greater than 5 × 10^9/L or an enlarged lymph node(s) (LDi > 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL) SLL participant must have presence of lymphadenopathy and absence of cytopenias caused by a clonal marrow infiltrate Participant must have relapsed or refractory CLL/SLL after receiving at least one prior line of therapy Participant must have 17p deletion, assessed by a central laboratory Participants (in Cohort 1) must have 17p deletion, assessed by a central laboratory Participants (in Cohort 2) must meet both of the following Relapsed/refractory disease to B-Cell Receptor Signaling Pathway Inhibitor (BCRI) treatment And either of the following: (a) relapsed/refractory disease to chemoimmunotherapy (CIT), or (b) ineligible to receive CIT, defined as having 17p deletion, or Cumulative Illness Rating Scale (CIRS) >6 or calculated creatinine clearance <70 mL/min Participant has undergone an allogeneic stem cell transplant Participant has developed Richter's transformation confirmed by biopsy Participant has prolymphocytic leukemia Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) Participant has previously received venetoclax Participant is known to be positive for Human Immunodeficiency Virus (HIV) Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug Participant has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug, or has not recovered to less than Common Toxicity for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy Any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy or targeted small molecule agents Investigational therapy, including targeted small molecule agents | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-99.0, Chronic Lymphocytic Leukemia (CLL) Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2 Participant has relapsed/refractory disease (received at least one prior therapy) Diagnosis of CLL that meets published 2008 Modified International Workshop on CLL National Cancer Institute Working Group (IWCLL NCI-WG) Guidelines and has an indication for treatment according to the 2008 Modified IWCLL NCI-WG Guidelines has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam) with or without 17p deletion or TP53 mutation may have been previously treated with a prior B-cell receptor inhibitor therapy Adequate bone marrow function Participant has developed Richter's transformation or Prolymphocytic leukemia (PLL) Participant has previously received venetoclax History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of adequately treated in situ carcinoma of the cervix uteri adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin previous malignancy confined and surgically resected (or treated with other modalities) with curative intent Active and uncontrolled autoimmune cytopenias (within 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), despite low dose corticosteroids Prior allogeneic stem cell transplant | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Anemia B-Cell Prolymphocytic Leukemia Grade 1 Follicular Lymphoma Grade 2 Follicular Lymphoma Grade 3a Follicular Lymphoma Hairy Cell Leukemia Lymphoplasmacytic Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Small Lymphocytic Lymphoma Richter Syndrome Phase I portion of the study: Histologically or flow cytometry confirmed diagnosis of B-CLL/SLL according to National Cancer Institute (NCI)-Working Group (WG) 1996 guidelines Phase I portion of the study: The following types of NHL as documented by medical records and with histology based on established by the World Health Organization (WHO) Mantle cell lymphoma (MCL) Follicular lymphoma (FL) grades 1-3a Lymphoplasmacytic lymphoma (LPL) Marginal zone lymphoma (MZL) CLL in Richter's transformation B-cell prolymphocytic leukemia Phase I portion of the study: Patients with histologically confirmed classical hairy cell leukemia (HCL) Prior therapeutic intervention with any of the following Therapeutic anticancer antibodies within 4 weeks (rituximab), except within 6 months for obinutuzumab or a similar investigational type II monoclonal antibody Radio or toxin-immunoconjugates within 10 weeks Inhibitors of BTK (ibrutinib), PI-3K (idelalisib), BH3-mimetic venetoclax, lenalidomide and other "targeted" therapy (including but not limited to investigational BTK and PI-3K inhibitors, etc.) within 6 half-lives (i.e., 36 hours for ibrutinib) All other chemotherapy, radiation therapy within 3 weeks prior to initiation of therapy SYK inhibitors at any time Inadequate recovery from adverse events related to prior therapy to grade =< 1 (excluding grade 2 alopecia and neuropathy) Chronic use of corticosteroids in excess of prednisone 30 mg/day or its equivalent | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-60.0, Lymphoma, Large B-Cell, Diffuse NCCN-IPI>1 Known IPI, cell of origin and DHL at time of diagnosis Negative pregnancy test Men must agree not to father a child during the therapy to 8 cycles R-CHOP/like, total of 8 x Rituximab CR, CRu Transformed lymphoma Secondary malignancy HIV positive Evidence of CNS involvement Cardiac dysfunction (systolic ejection fraction <50%) Creatinine > 2.0 mg/dl | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 3.0-70.0, Acute Lymphoblastic Leukemia Immune System Diseases Immunoproliferative Disorders Cell Procurement Written informed consent for procurement signed by subject/legal guardian of pediatric subject and HIPAA authorization Age 3-17 years of age for pediatric subjects (weight must be ≥10 kg), ≥18-70 years of age for adults at time of consent Karnofsky score >60% (≥16 years old), Lansky performance score of >60% (<16 years old) Relapsed or refractory (R/R) precursor B cell ALL d or greater bone marrow relapse, or Any bone marrow relapse >100 days after allogeneic stem cell transplant, or Primary refractory ALL defined as no complete response (CR) after 2 cycles of standard of care chemotherapy regimen, or For adult subjects: 1st bone marrow relapse with 1st CR <1 year, or CR1 ≥1 year and refractory to ≥1 cycle of therapy for relapse Subjects with isolated non-CNS extramedullary disease will be eligible as long as the time-of-remission (above) are met and biopsy for extramedullary disease confirms CD19 expression Cell Procurement Subject with relapsed fulminant CD19+ ALL rapidly progressing with circulating lymphoblasts that are rising in proportion to >50% of circulating white blood cells Lumbar puncture must be performed prior to procurement and subject with evidence of CNS3 disease will be excluded from study entry. Subject with concurrent CNS3 disease and bone marrow relapse who responded to CNS-directed therapy prior to enrollment/LD allowed to participate. Subject with CNS2 disease and concurrent bone marrow relapse are eligible. Intrathecal chemotherapy will be allowed to continue between cell procurement and LD Pregnant/breastfeeding (Note: breast milk cannot be stored for future use if collected while the mother is being treated on study) Has known active and/or progressive additional malignancy requiring treatment; exceptions basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, other cancer for which the subject has been disease-free for ≥5 years Subject must not have tumor in a location where enlargement could cause airway obstruction Subject may not have an oxygen requirement as defined by pulse oximetry of <90% on room air Subject must not have left ventricular ejection fraction of <40% (shortening fraction <27% for pediatric subjects) as measured by echo or MUGA Patient with the following infections will be excluded: active HIV, HTLV, HBV, HCV. Note: To meet subjects must not be positive for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for Hep B surface antigen, or negative for HCV antibody or HCV viral load Patient on treatment for other active uncontrolled infections with resolution of signs/symptoms are not excluded. Non-influenza, non-RSV, isolated upper respiratory infections are not excluded. Other active uncontrolled infections will be excluded | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Cholangiocarcinoma only those positive for CA19.9 pregnant and lactating females | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 50.0-90.0, Osteoarthritis Pain Syndrome Intra-articular Injection According to radiographic findings, patients who are suffering from knee OA for over 3 months have to be stage II-IV according to the Kellgren-Lawrence (KL) grade by a senior radiologist. The diagnosis of symptomatic knee OA is based on American Rheumatism Association classification for knee osteoarthritis are the diagnosis of rheumatoid arthritis or other inflammatory OA, presence of trauma or pain-causing diseases, treatment with oral medications in recent 3 days, physiotherapy and intra-articular injection of HA or CS in the past 6 months. Participants who are allergic to any of the medications used in this study or diagnosed with current systemic infection are also excluded | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Hemophilia B for patients Were screened and consented for the AskBio009-101study at any point in time Are able to speak and understand English Are between ages of 18 and 75 Are physically able to participate in a one-hour phone interview Consented into this study independently of the AskBio009-101 study for patients N/A for investigators and coordinators Worked at a site as an investigator or study coordinator that consented a patient into the AskBio009-101 trial at any point in time, including those that no longer work at a AskBio009-101 site Are able to speak and understand English Are between ages of 18 and 75 Are physically able to participate in a one-hour phone interview for investigators and coordinators Not directly involved in the consent process at the gene therapy site | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Richter Syndrome Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2008 (Hallek et al, 2008) with biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's Syndrome Age greater than or equal to 18 years. Because CLL and Richter's Syndrome are extremely rare in persons <18 years of age, children are excluded from this study ECOG performance status <2 (see Appendix A) Patients must meet the following hematologic at screening, unless they have significant bone marrow involvement of their malignancy confirmed on biopsy Absolute neutrophil count ≥1000 cells/mm3 (0.5 x 109/L). Growth factor allowed to achieve Platelet count ≥40,000 cells/mm3 (40 x 109/L) independent of transfusion within 7 days of screening Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows Creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min using 24-hour urine collection for creatinine clearance Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN Bilirubin ≤ 1.5 × ULN Patients with the Hodgkin variant transformation of CLL will be excluded History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to the chemotherapy drugs used in this study (see Appendix D), unless the antibody can be given through a desensitization program in consultation with an allergist Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of chemotherapy, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: --Any anti-cancer therapy including chemotherapy, biologic agents for anti-neoplastic treatment (e.g. monoclonal antibodies) or radiotherapy, investigational therapy, including targeted small molecule agents. Patients who are currently receiving treatment with ibrutinib or acalabrutinib may continue this agent until the day prior to starting venetoclax, to reduce the risk of tumor flare on treatment cessation Received previous treatment with R-CHOP, R-EPOCH, or R-hyper-CVAD History of other malignancies, except Malignancy treated with curative intent and with no known active disease present before the first dose of study drug and felt to be at low risk for recurrence by treating physician Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Low-risk prostate cancer on active surveillance Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.) within 28 days of the first dose of study drug | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Have received at least one dose of Obinutuzumab as per local label and clinical practice Included in clinical trial | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Chronic Hepatitis C (Disorder) Positive serum Anti-HCV antibody or serum HCV-RNA, CHC patients without any treatment Patient has a history of clinical signs/symptoms of hepatic decompensation (Child-Pugh Grade B or C) or ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. Patient has a history of hepatocellular carcinoma (HCC) or suspected symptoms of HCC, such as suspicious foci on imaging studies and/or serum alpha-fetoprotein (AFP)>50ng/mL. Patient has received IFN or other immunomodulatory treatment within 52 weeks before Screening. Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir. Patient has a medical condition that requires frequent use of systemic corticosteroids, however topical and inhaled corticosteroids are allowed. Patient has used hepatotoxic drugs within one month. Patient has overtaken alcohol (>40g/day) or abused illicit drugs in recent one year. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test. Patients who co-infected with HAV, HBV, HDV, HEV,HIV(human immunodeficiency virus ) Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis C (e.g., alcoholism, autoimmune hepatitis). History of malignancy of any organ system | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Crohn Disease Ulcerative Colitis Intestinal Helminthiasis The included volunteer is a researcher within parasitology with main focus on Trichuris trichiura and Trichiura suis. He planned to infect himself and contacted our department with the purpose of being monitored during this infection for safety (medical supervision) and research reasons. The only clinical criterion for his in the study was that he was healthy | 0 |
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