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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): 18.0-999.0, Non-Hodgkin's Lymphoma Follicular Lymphoma Diffuse Large Cell Lymphoma Mantle Cell Lymphoma Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia SLL / CLL 1. Diagnosis of B-cell SLL/ CLL including Lymphocytosis of monoclonal B-cells co-expressing ≥ one B-cell marker (CD19, CD20, or CD23) and CD5 in peripheral blood or lymph node AND Bone marrow with ≥ 30% mononuclear cells having the SLL / CLL phenotype. 2. Presence of at least ONE single accessible AND palpable lymph node in the cervical, supraclavicular, axillary, or inguinal regions. The size of the lymph nodes must be larger than 2x2 cm in the horizontal and perpendicular axes. 3. Intermediate or High risk, poor prognosis SLL / CLL 4. Indication for treatment as defined by the NCI Working Group Guidelines Massive (i.e. > 6 cm below the left costal margin) or progressive splenomegaly OR Massive lymph nodes or nodal clusters (i.e. > 10 cm in longest diameter), 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 Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and / or thrombocytopenia Pregnant or nursing women 2. Treatment with chemotherapy or monoclonal antibody within 28 days prior to entering the study. 3. Treatment with chemotherapy or monoclonal antibody during the time of participation in this trial. 4. Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification 5. Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, COPD). 6. Participation in any investigational drug study within 28 days prior to ISF35 administration. (Patient must have recovered from all acute effects of previously administered investigational agents). 7. Evidence of aggressive or highly aggressive lymphoma or Richter's transformation based on WHO/REAL classification criteria[1] 8. Any T cell lymphoma. 9. History of malignancy other than NHL or SLL/CLL or within five years of registration, except patients with adequately treated basal, squamous cell carcinoma or localized cervical cancer. 10. Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis. 11. Any illness or condition that in the opinion of the Investigator may affect safety of treatment or evaluation of any the study's endpoints | 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): 10.0-999.0, Nasopharyngeal Carcinoma Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease in whom the EBV-genome or antigens have been demonstrated in tissue biopsy samples Age 10 years or older Life expectancy of 8 weeks or more Karnofsky or Lansky score of 50 or more Normal bilirubin level (per institutional standard) AST and ALT 1.5 x or less upper limit of normal Alk Phos level less than 2.5 x upper limit of normal ANC greater than 1500 cells/ul Hgb 8.0 or greater Platelets 100,000 cells/ul or more Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research Prior allergic reaction to the study drugs used in this protocol or other drugs formulated with polysorbate 80 Known HIV positive subjects since treatment may be significantly immunosuppressive Women who are breast-feeding Severe intercurrent infection Patients, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of 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, Indolent Lymphoma Need for therapy in patients with relapsed/refractory patients Histological proven diagnosis of an indolent B-cell lymphoma according to the World Health Organization (WHO) classification belonging to one of the following entities follicular lymphoma mantle cell lymphoma lymphoplasmacytic lymphoma nodal or splenic marginal zone lymphoma measurable disease lymphoma specific therapy in the last four weeks WHO performance grade 0, 1 or 2 Patients suitable for high dose therapy Transformation in high grade lymphoma Leukocytes < 1,5/nl or platelets < 100/nl (except due to lymphoma) | 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): 0.0-35.0, High Risk Solid Tumors Recurrent Solid Tumors Patients diagnosed with high risk recurrent or refractory solid tumors following initial chemotherapy 2. Tumor must be sensitive to chemotherapy (maximum 8 cycles) and/or radiation defined as a greater than 50% reduction in size of the primary and/or metastatic sites. 3. Patients who are under 35 years of age. 4. Patients with a life expectancy of at least 8 weeks and performance status (Karnofsky or Lansky score) of at least 70%. 5. Patients who are acceptable candidates for peripheral blood stem cell transplantation based on their pre-transplant evaluation Patients will not be excluded based on sex, race. 2. Patients with central nervous system tumors are not eligible for this protocol. 3. Patients have significant functional deficits in major organs which would interfere with successful outcome following PBSCT. 4. Patients who have been treated for infections must have appropriate responses as documented by negative cultures and/or a normal radiographic examination. 5. Patients may not have active CNS disease or marrow involvement with the tumor at the time of transplant. 6. Patients with disease progression after tandem PBSC #1 will not be eligible for tandem PBSC #2. 7. Patients will be excluded if they are women of childbearing potential who are currently pregnant (HCG+) or who are not practicing adequate contraception. 8. Patients who have had a previous stem cell transplant | 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, Non-Hodgkin's Lymphoma Age ≥ 18 years Biopsy proven intermediate grade NHL No previous chemotherapy At least 4 courses of R-CHOP at maximal doses are planned An informed consent Do not meet all | 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, Lymphoma Histologically confirmed CD20-positive diffuse large B-cell non-Hodgkin lymphoma (DLBCL) according to the current WHO classification, including all morphological variants Newly diagnosed disease Bulky stage IA-IV disease No non-bulky stage IA disease Measurable disease Not eligible for CHOP chemotherapy due to impaired cardiac function Cardiac status that does not allow the administration of 8 courses of R-CHOP chemotherapy, as defined by 1 of the following Ejection fraction less than 50% as assessed by either ECHO or MUGA scan NYHA class III-IV No high-grade transformation of low-grade lymphoma | 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, Inflammation Necrosis Healthy children (ASA PS 1) Children presenting one or more primary molar with pulp inflammation or necrosis due to carious lesion and indicated for endodontic therapy Lost to follow-up | 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): 65.0-999.0, Chronic Lymphocytic Leukemia Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following Minimum threshold peripheral lymphocyte count of 5 x 10^9/L (CLL variant) OR palpable adenopathy > 1 cm or palpable splenomegaly 9small lymphocytic lymphoma [SLL] variant) Immunophenotypic demonstrations of a population of B-lymphocytes (as defined by CD19+) that are monoclonal (by light-chain exclusion) AND have ≥ 3 of the following characteristics CD5+ CD23+ Dim surface light chain expression Dim surface CD20 expression FISH analysis is negative for immunoglobulin heavy chain/cyclin D1 gene (IGH/CCND1) and/or immunostaining is negative for cyclin D1 expression (to mantle cell lymphoma) Progressive, symptomatic CLL, defined by at least one of the following Weight loss > 10% within the past 6 months attributable to progressive CLL (grade 2 or higher) Prior treatment for CLL Massive splenomegaly > 6 cm below left costal margin, at rest, on clinical examination Lymphadenopathy > 5 cm in any diameter New York Heart Association class III or IV heart disease Recent myocardial infarction (within the past month) Uncontrolled infection Infection with the human immunodeficiency virus (HIV/AIDS) Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive) Positive hepatitis C serology Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia | 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): 18.0-55.0, Musculoskeletal Pain Signed and dated informed consent prior to participation Subjects in good health as determined by the Investigator Age 18-55 Willing to abstain from any physical therapy, hard physical work, exercise or sauna during the study observation period (Screening to Final Visit) For females, subjects of childbearing potential (including peri-menopausal women who have had a menstrual period within 1 year) must be using appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly, such as implants, injectables, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner). Oral contraceptive medications are allowed in this study. Female subjects, who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) are also allowed for participation Participation in another clinical study within the last 30 days and during the study Subjects who are inmates of psychiatric wards, prisons, or other state institutions Investigator or any other team member involved directly or indirectly in the conduct of the clinical study Pregnancy or lactation Alcohol or drug abuse Malignancy within the past 2 years with the exception of in situ removal of basal cell carcinoma Skin lesions, dermatological diseases or tattoo in the treatment areas Known hypersensitivity or allergy (including photoallergy) to NSAID´s including celecoxib, sulfonamides and ingredients used in pharmaceutical products and cosmetics including galactose Varicosis, thrombophlebitis and other vascular disorders of the lower extremities Major traumatic lesions (e.g. fracture, tendon or muscle ruptures) of the musculo-skeletal system of the lower limbs | 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, HIV Infection Liver Failure Evidence of Liver Transplantation Age ≥ 18 Documented HIV-1 infection, hepatitis B or C co-infection is allowed Plasma viral load at screening visit below 50 copies per mL for at least 6 months Patient with severe liver failure (Meld Score ≥ 15 and/or refractory ascites and/or haemorrhage of digestive tract and/or hepatic encephalopathy) for taking part into period 1 Patient eligible for the liver transplant waiting list or immediate post transplantation for taking part into period 2 Abstinence from alcohol intake for at least 6 months (WHO norm) Withdrawal from intravenous drug use for at least 6 months (methadone substitution is permitted) No ongoing class C opportunistic infection (1993 CDC classification) Patient whose clinical and immunovirological condition allows triple therapy with raltegravir + 2 NRTI or raltegravir + NRTI + enfuvirtide Patient whose HIV population, according to cumulative genotypes carried out on viral RNA together with treatment history (if available and interpreted as per the ANRS-AC11 algorithm version no.19) does not present a profile of mutations associated with resistance to raltegravir and is sensitive to at least two fully active* agents selected among nucleoside/nucleotide reverse transcriptase analogs NRTI (abacavir, lamivudine, emtricitabine, tenofovir) or enfuvirtide *An ARV agent is considered to be fully active if the cumulative genotypes do not show any mutation associated with resistance or any mutation associated with "possible resistance" More than two virological failures during antiretroviral treatment Currently receiving treatment with an agent in development (apart from an authorization for temporary use) Plasma viral load at screening visit ≥ 50 copies per mL during at least the last 6 months Pregnant women, or women liable to become pregnant, breast-feeding women, no contraception, or refusal to use contraception All conditions (including but not limited to alcohol intake and drug use) liable to compromise, in the investigator's opinion, the safety of treatment and/or the patient's compliance with the protocol Patient not having any effective options for NRTI +/ enfuvirtide (defined in the criteria) Ongoing treatment with interferon-alpha or ribavirin for hepatitis C Concomitant medication including one or more agents liable to induce UGT1A1 and reduce raltegravir concentrations anti-infective agents: rifampicin/rifampin | 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): 0.5-999.0, HIV Infection Rheumatic Disease Cancer Transplant Pediatrics medically recommended influenza A(H1N1) immunization signed informed consent failure or refusal to provide sufficient blood for antibody determination | 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): 18.0-59.0, First Episode Psychosis Aged 18-59 years and meet DSM-IV diagnostic for first episode of schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder NOS as assessed by using the Structured Clinical Interview for DSM-IV, research version Meeting DSM-IV for another axis I diagnosis, including substance abuse or dependence Needing another nonantipsychotic psychotropic medication at enrollment Having a serious or unstable medical illness Pregnant or lactating women or women without adequate contraception will be 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): 18.0-999.0, Metastatic Melanoma ENTRY Locally advanced or metastatic melanoma Measurable Histologically or cytologically confirmed Surgically incurable HLA-A2 positive and tumors that present HLA-A2.1/p53aa264-272 complexes PRIOR/CONCURRENT If prior Proleukin treatment, must have had clinical benefit No prior systemic cytotoxic chemotherapy for melanoma No concurrent radiotherapy, chemotherapy, or other immunotherapy More than 4 weeks since prior major 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): 18.0-999.0, Hodgkin Lymphoma Diffuse Large B-Cell Lymphoma Previously treated orrefractory classical large B-cell lymphomas, Grey-zone lymphoma and Hodgkin lymphoma, including Lymphocyte predominant Hodgkin Lymphoma (LPHL). 2. Confirmed pathological diagnosis by the Laboratory of Pathology, NCI. 3. Age greater than or equal to 18 years. 4. ECOG performance 0-2 5. Laboratory tests: ANC greater than or equal to 1000/mm(3), platelet greater than or equal to 75,000/mm(3). Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 ml/min; AST and ALT less than or equal to 5 times the ULN. Total bilirubin < 2.0 mg/dl except < 5mg/dL in patients with Gilbert s (as defined as > 80% unconjugated hyperbilirubinemia without other known cause); unless impairment due to organ involvement by lymphoma Active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If ECHO is obtained, the LVEF should exceed 40%. 2. HIV positive, because of the unknown effects of combined therapy with chemotherapy and an immunosuppressive agent on HIV progression. 3. Female subject of child-bearing potential not willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and two years beyond treatment completion. 4. Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotrophin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without childbearing potential. 5. Male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion. 6. Invasive or active malignancy in past 2 years. 7. Serious concomitant medical illnesses that would jeopardize the patient s ability to receive the regimen with reasonable safety. 8. Active CNS lymphoma. These patient have a poor prognosis and because they frequently develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events. 9. Systemic cytotoxic therapy within 3 weeks of treatment | 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, Ovarian Cancer Non Small Cell Lung Cancer Prostate Cancer Colorectal Cancer Gastric Cancer Esophageal Cancer Cancer of Head and Neck Diagnosis of ovarian, non-small cell lung, prostate, colorectal, gastroesophageal cancer (adenocarcinoma of the esophageal cancer, stomach, or gastroesophageal junction), or squamous cell cancer of the head and neck Have measurable disease defined by Response Evaluation in Solid Tumors (RECIST) 1.1 guidelines (except prostate cancer participants) Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Are willing to follow study procedures for the duration of the study Are willing to use an approved contraceptive method during treatment and for 3 months after discontinuation of study treatment Have a serious preexisting medical condition that would preclude participation in the study Are pregnant or lactating Have received treatment within 28 days of first dose of LY2523355 with a drug that has not received regulatory approval for any indication Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases Have a second active primary malignancy or a history of a second malignancy requiring cytotoxic therapy Have QTc interval greater than 470 millisecond (msec) or intraventricular conduction delay (IVCD) with QRS greater than 120 msec on screening electrocardiogram (ECG) Have active symptomatic fungal, bacterial, and/or known viral infection including active human immunodeficiency virus (HIV) or viral (A, B, C) hepatitis Participants with pneumonia, evidence of obstructive pneumonitis, other respiratory infections, or infection from other sources are to 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): 18.0-999.0, Chronic Lymphocytic Leukemia Clinical diagnosis with CLL Clinical decision made to initiate first-line therapy, second-line therapy or subsequent line of therapy prior to enrollment into the ConnectTM CLL registry, but within 2 months of enrollment Age≥18 years Willing and able to provide signed informed consent Willing and able to complete patient assessment questionnaires either alone or with minimal assistance from caregivers and/or trained site personnel Participation in a clinical study in which study treatment is blinded Patient condition is considered terminal (i.e.<6 months to live) | 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, Asthma Patients who have given their informed consent and expressed interest in participating in the study Asthmatic Patients Patients with communication difficulties Persons who obtain symbicort but not for their own use Patients with other major diseases: Heart problems, COPD, lung cancer, AIDS Patients with a respiratory infection Patients with seasonal asthma Pregnant women Patients who have previously participated in a health education study in asthma | 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, Hairy Cell Leukemia (HCL) Chronic Lymphocytic Leukemia (CLL) Non-Hodgkins Lymphoma (NHL) Cutaneous T Cell Lymphoma (CTCL) Adult T Cell Lymphoma (ATL) Patients may have a diagnosis of hematologic malignancy, including HCL, CLL, CTCL, ATL, NHL, ALL, or solid tumor, including mesothelioma. These patients would not be excluded if they were in complete remission or thought to be cured of their malignancy Patients and normal volunteer donors must be at least 18 years of age and able to give informed consent. Informed consent will be waived for patient samples transferred from other protocols For patients undergoing leukapheresis for research purposes, the hematocrit must be at least 28% and the platelet count at least 50,000/mm(3) of Women and Minorities-Both men and women and members of all races and ethnic groups are eligible for this trial Desire of the patient or normal donor not to submit samples FOR Heart, lung, kidney disease, or bleeding disorders Diagnosis of cancer Hepatitis since age 11 Pregnancy History of HIV infection or AIDS History of high-risk activities for exposure to the AIDS virus, including Receipt of money or drugs in exchange for sex in the past 5 years Use of needles to take drugs, steroids, or anything not prescribed by a physician in the past 5 years | 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, Cystic Fibrosis Gender: Male or female (non-pregnant, non-lactating) Cystic fibrosis documented by a compatible clinical and radiographic presentation, and sweat chloride > 60 mEq/l or 2 disease causing CFTR mutations Severity of Disease: 1. Must have FEV1 of greater than or equal to 50% of predicted at the screening visit. 2. Must have an oxygen saturation of >92% on room air as determined by pulse oximetry at the screening visit Patient or legally authorized representative agrees to the patient/individual's participation in the study by signing and dating the informed consent form after the nature of the study has been fully explained and all questions have been satisfactorily answered Unstable lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 >15% below recent (within 6 months) clinical measurements; or a significant new finding on chest radiograph (pneumothorax, lobar/segmental collapse) not considered a part of the usual, chronic progression of CF lung disease Patients unable or unwilling to be withdrawn from hypertonic saline therapy, dornase alfa, or N-acetylcysteine 3 days prior to and for the duration of each Baseline and Treatment Period will be excluded Patients unable to withhold use of long-acting bronchodilators (i.e., Salmeterol, Advair, Formoterol), anti-cholinergics, and vest therapy 12 hours prior to and for the duration of each treatment period Patients unable to withhold short-acting bronchodilator 6 hours prior to and for the duration of each treatment period except as prescribed by the study protocol Patients that have received an investigational drug or therapy during the preceding 30 days Patients that have had radiation exposure within the past year that would cause them to exceed Federal Regulations by participating in 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): 18.0-999.0, Non Hodgkin's Lymphoma NHL Aggressive NHL Diffuse Large B-cell Lymphoma Male or female, >18 years old Histological diagnosis of CD20+ B-cell NHL, with DLBCL or other aggressive lymphomas by WHO lymphoma including mantle cell lymphoma and transformed follicular lymphoma Failed at least one prior standard treatment regimen for NHL If DLBCL, either received, ineligible for or refused high-dose chemotherapy with stem cell transplant Measurable NHL disease by CT, with at least one lesion >1.5 cm in one dimension Adequate performance status (>70 Karnofsky scale, 0-1 ECOG)* with an estimated life expectancy of at least 6 months Laboratory parameters Adequate hematology (Hemoglobin >/= 10 g/dL, ANC >/= 1.5 ´ 109/L, platelets >/=100 x 109/L) without ongoing transfusional support Adequate renal and liver function (creatinine and bilirubin </= 1.5 x IULN; AST and ALT </= 2.5 x IULN) Otherwise, <Grade 1 toxicity at study entry by NCI CTC version 3.0 Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test NCI CTC Grade 3 or 4 infusion reaction to prior anti-CD20 antibodies (rituximab, veltuzumab, etc.) A known anti-antibody response to prior antiCD20 antibodies (HACA positive, HAHA positive, etc) Prior radioimmunotherapy, including Zevalin or Bexxar Prior high-dose chemotherapy with peripheral blood stem cell transplant Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested and negative Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of symptomatic CNS metastases or carcinomatous meningitis Rituximab or veltuzumab resistant, defined as having progressed during or within 6 months of any prior rituximab or veltuzumab treatment Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter Bone marrow involvement ≥25% | 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, Hepatic Encephalopathy Patients diagnosed as having cirrhosis of liver at the Inpatient/Outpatient Liver Clinic of Department of Hepatology, Chandigarh, will be candidates for enrollment The diagnosis of cirrhosis of liver will be based on clinical, biochemical, and ultrasonographical or liver histological data Alcohol intake during the past 6 weeks Hepatocellular carcinoma Previous transjugular intrahepatic portosystemic shunt or shunt surgery Significant comorbid illness such as heart, respiratory, or renal failure Any neurologic diseases such as Alzheimer's disease, Parkinson's disease, and nonhepatic metabolic encephalopathies Patients on psychoactive drugs, such as antidepressants or sedatives Those who restart alcohol consumption during follow-up will also 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): 18.0-999.0, Chronic Lymphocytic Leukemia Must be 18 years of age Must meet the clinical and laboratory for B-CLL (i.e., compatible clinical history and physical exam, presence of lymphocytosis, i.e., >10,000 lymphocytes / mm3, evidence for a monoclonal population of CD5+/CD19+/CD23+ cells in the periphery that have dim surface membrane lg with L chain isotype restriction) All patients will be staged according to the system of Rai. Only new onset patients who are not receiving therapy will be entered into the heavy water leukemic cell turnover studies Patients hospitalized for an acute medical problem, related or not to their leukemia, within 4 weeks of enrollment A history of a second malignancy involving the hematopoietic system, or the need for extensive chemotherapy for any second malignancy; patients with active immunologic disorders (e.g., HIV and AIDS), especially autoimmune problems (e.g., autoimmune hemolytic anemia of any cause other than B-CLL) Patients with impaired decision-making capabilities, e.g. dementia, psychosis, alcoholism, and illicit drug use will also be 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): 18.0-99.0, Lymphoma, Mantle-cell CLL (Chronic Lymphocytic Leukemia) Monoclonal B-Cell Lymphocytosis Healthy Volunteers Small Lymphocytic Lymphoma (MBL, CLL/SLL, MCL group) 4.1.1.<TAB>Diagnosed with MBL, CLL/SLL, or MCL 4.1.2.<TAB>Greater than or equal to 18 years of age 4.1.3.<TAB>Neutrophil count (ANC) greater than or equal to 1000/mcL 4.1.4.<TAB>Platelet count greater than or equal to 50K/mcL (MBL, CLL/SLL, MCL group) 4.2.1.<TAB>Concomitant use of agents that have been described to affect the biology and/or proliferation rate of CLL cells but are not approved or accepted therapies for CLL, SLL, MCL, or MBL PDE-inhibitors (e.g. sildenafil, theophylline) Immunosuppressive agents (e.g., prednisone, cyclosporin-A, rapamycin) Green Tea extract (more than 2 cups per day) Cox-2 inhibitors 4.2.2.<TAB>Chronic or current clinically significant infection, including HIV or uncontrolled infection 4.2.3.<TAB>Receiving concurrent anticancer therapies 4.2.4.<TAB>Women who are pregnant or nursing, as well as women of childbearing potential who are unwilling to use a an agreed upon form of contraception for the duration of participation in this study 4.2.5<TAB>Sexually active males who are unwilling to follow the strict contraception requirements described in this protocol. 4.2.6<TAB>Inability to understand the investigational nature of the study, inability to provide informed consent (Healthy volunteer group) 4.3.1<TAB>Health status will be confirmed by brief History and Physical Exam and blood work 4.3.2<TAB>Greater than or equal to 18 years of age 4.3.3<TAB>CBC and coagulation panel within the expected normal ranges for the subject (Healthy volunteer group) 4.4.1.<TAB>Concomitant use of agents that have been described to affect the biology and/or proliferation rate of CLL cells PDE-inhibitors (e.g. , slidenafil, theophylline) Immunosuppressive agents (e.g., cyclosporin-A, rapamycin) Green Tea extract (more than 2 cups per day) Cox-2 inhibitors <TAB> 4.4.2.<TAB>Women who are pregnant or nursing, as well as women of childbearing potential who are unwilling to use an agreed upon form of contraception for the duration of study participation. 4.4.3<TAB> Sexually active males who are unwilling to follow the strict contraception requirements described in this protocol. 4.4.4.<TAB>Inability to understand the investigational nature of the study, inability to provide informed consent | 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 Tuberculous Mediastinal Lymphadenopathy All patients with mediastinal lymphadenopathy of unknown etiology 2. All patients signed informed consent before the procedure Age less than 18 years 2. Bleeding diathesis (INR>1.4 or platelet count<10k/mcl) | 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): 10.0-83.0, Lymphadenopathy Patients with previously untreated neck masses underwent neck US The neck mass was not lymph node No US-FNA cytology result | 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): 0.5-75.0, Lymphoma Leukemia Myelodysplastic Syndrome First-degree related donor who is at minimum HLA haploidentical Eligible diagnoses: 1. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed during multiagent therapy, failed at least two prior therapies (excluding single agent rituximab and single agent steroids), or in the case of lymphoma undergone histological conversion Follicular grade 1 or 2 lymphoma Follicular lymphoma not otherwise specified Marginal zone (or MALT) lymphoma Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia Hairy cell leukemia Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) Prolymphocytic leukemia Low grade B-cell lymphoma, unspecified Pregnant or breast-feeding Uncontrolled infection Note: Infection is permitted if there is evidence of response to medication. of HIV infected patients will be determined on a case-by-case basis Any previous BMT within 3 months prior to start of conditioning Active extra-medullary leukemia or known active Central Nervous System (CNS) involvement by malignancy. Such disease treated into remission is permitted | 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, Symptomatic Waldenstroms Macroglobulinaemia At least 18 years of age Diagnosis of WM histologically confirmed on bone marrow biopsy Detectable IgM paraprotein >5 g/L Less than 3 lines of prior therapy for WM Full blood count within 4 weeks prior to screening shows ANC >1.0 x109/l AND platelet count >50 x109/l Therapy indicated due to development of one or more of the following: 1. symptomatic anaemia 2. hyperviscosity symptoms 3. rapidly rising paraprotein of >25% or >5g/l over 3 months 4. splenomegaly 5. bulky lymphadenopathy 6. B symptoms or paraneoplastic phenomena, which, in the opinion of the investigator are the result of progressive WM Life expectancy >12 months ECOG < 3 Able to provide informed consent Ability to understand the requirements of the study, provide written informed consent, including consent for the use and disclosure of research-related health information, and comply with the protocol procedures, including required study visits Prior therapy with belimumab Pregnant or breast feeding Chemotherapy, immunotherapy or biological therapy within 4 weeks of enrolment. Therapeutic plasma exchange can continue see section 3.1.4 Creatinine clearance (calculated by Cockcroft-Gault) < 60ml/min Bilirubin >2x ULN, ALT >2x ULN History of an allergic or anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies, a history of severe allergic reaction to drugs, food, or insects requiring medical intervention, or a history of hypersensitive triad (having all 3 features of allergic rhinitis with nasal polyps, asthma, and aspirin sensitivity) Prior opportunistic infection including tuberculosis or atypical mycobacterial infection, multi-dermatome Herpes Zoster or Pneumocystis pneumonia or invasive fungal infection (not including oral or vaginal candidiasis or superficial dermatophytes) Active infection with hepatitis B, hepatitis C or HIV or historically positive test or test positive at screening for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody History of organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant | 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): 18.0-99.0, Small Lymphocytic Lymphoma CLL (Chronic Lymphocytic Leukemia) Histologically confirmed CLL or SLL as defined by the following B-lymphocytosis greater than 5000 cells/micro L (may be less than 5000 cells/micro L if lymphadenopathy is present with histologic confirmation of lymph node involvement by SLL) Immunophenotypic profile consistent with CLL as demonstrated by flow cytometry Appropriate immunophonotype (CD5/19/23+) Clonality of lymphocytosis confirmed by flow cytometry large lymphocytes less than 55 % of blood lymphocytes Active disease as defined by at least one of the following Weight loss greater than or equal to10 percent within the previous 6 months Extreme fatigue Fevers of greater than 100.5 degree F for greater than or equal to 2 weeks without evidence of infection Night sweats for more than one month without evidence of infection Prior monoclonal antibody therapy with agents having anti-CLL activity Prior cytotoxic chemotherapy with agents having anti-CLL activity (Fludarabine, Cyclophosphamide, Bendamustine, Chlorambucil) Transformed CLL Active autoimmune hemolytic anemia or thrombocytopenia Any medical condition that requires the chronic use of corticosteroids Active or latent Hepatitis B infection HIV infection Severe chronic obstructive pulmonary disease, severe cardiac disease, or other uncontrolled medical condition that would, in the opinion of the principal investigator, place the subject at an unreasonable risk of life-threatening adverse events due to chemoimmunotherapy ECOG performance status 3 or worse Creatinine greater than or equal to 2 mg/dL or creatinine clearance less than or equal to 30 mL/min Bilirubin greater than or equal to 2 mg/dL or active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment) Female patients: Current pregnancy or unwilling to take oral contraceptives 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. Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements. Unable to understand the investigational nature of the study or give informed consent | 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, Healthy Is the individual a healthy, normal adult man or non-child bearing potential woman who volunteers to participate? Is s/he at least 18 years of age? Is his/her BMI between 19 and 30, inclusive? Is s/he considered reliable and capable of understanding his/her responsibility and role in the study? Has s/he provided written informed consent? Does the individual have a history of allergy or hypersensitivity to zonisamide or sulfonamides? Does s/he have clinically significant laboratory abnormalities that would interfere with the conduct or interpretation of the study or jeopardize his/her safety? Does s/he have significant history or clinical evidence of auto-immune, cardiovascular, gastrointestinal, hematological, hematopoietic, hepatic, neurological, ongoing infection, pancreatic, or renal diseases that would interfere with the conduct or interpretation of the study or jeopardize his/her safety? Does s/he have serious psychological illness? Does s/he have significant history (within the past year) or clinical evidence of alcohol or drug abuse? Does s/he have a positive urine drug screen, or a positive HIV-1, or hepatitis B or C screen, or a positive pregnancy test? Has s/he consumed grapefruit or grapefruit juice during the 7-day period preceding study initiation? Is s/he unable to refrain from the use of alcohol or xanthine-containing foods or beverages during periods beginning 48 hours prior to study drug administration and ending when the last blood sample has been taken? Has s/he used any prescription drug during the 14-day period prior to study initiation, or any OTC drug during the 72-hour period preceding study initiation? Is s/he unable to refrain from the use of all concomitant medications during the study? Has s/he donated or lost blood, or participated in a clinical study which involved the withdrawal of a large volume of blood (480 mL or more), during the six week period preceding study initiation? | 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, Healthy Is the individual a healthy, normal adult man or non-child bearing potential woman who volunteers to participate? Is s/he at least 18 years of age? Is his/her BMI between 19 and 30, inclusive? Is s/he considered reliable and capable of understanding his/her responsibility and role in the study? Has s/he provided written informed consent? Does the individual have a history of allergy or hypersensitivity to zonisamide or sulfonamides? Does s/he have clinically significant laboratory abnormalities that would interfere with the conduct or interpretation of the study or jeopardize his/her safety? Does s/he have significant history or clinical evidence of auto-immune, cardiovascular, gastrointestinal, hematological, hematopoietic, hepatic, neurological, ongoing infection, pancreatic, or renal diseases that would interfere with the conduct or interpretation of the study or jeopardize his/her safety? Does s/he have serious psychological illness? Does s/he have significant history (within the past year) or clinical evidence of alcohol or drug abuse? Does s/he have a positive urine drug screen, or a positive HIV-1, or hepatitis B or C screen, or a positive pregnancy test? Has s/he consumed grapefruit or grapefruit juice during the 7-day period preceding study initiation? Is s/he unable to refrain from the use of alcohol or xanthine-containing foods or beverages during periods beginning 48 hours prior to study drug administration and ending when the last blood sample has been taken? Has s/he used any prescription drug during the 14-day period prior to study initiation, or any OTC drug during the 72-hour period preceding study initiation? Is s/he unable to refrain from the use of all concomitant medications during the study? Has s/he donated or lost blood, or participated in a clinical study which involved the withdrawal of a large volume of blood (480 mL or more), during the six week period preceding study initiation? | 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 Syndrome Signed written informed consent prior to performing any study-specific procedures Patients with B-CLL and newly diagnosed not previously treated and biopsy proven DLBCL Richter's transformation Computerized tomography (CT) scan performed within 6 weeks prior to starting treatment ECOG (Eastern Cooperative Oncology Group) Performance Status of 0, 1, 2 or 3 Age 18 years and over CHOP or CHOP-like anthracycline containing treatment for DLBCL within 6 months prior to registration Known central nervous system (CNS) involvement of B-CLL Any malignancy that requires active treatment with the exception of basal cell carcinoma and non-invasive squamous cell carcinoma Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis Subjects meeting any of the following must not be enrolled in the study Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg (the surface antigen of the Hepatitis-B-Virus). In addition, if negative for HBsAg but HBcAb (Hepatitis B core Antibody) positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. Consent will be sought prior to any test being performed Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease History of significant cerebrovascular disease in last 6 months Known Human immunodeficiency virus (HIV) positive | 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, Hepatitis C HIV A subject must satisfy all of the following to be eligible to participate in this study: 1. Latino ethnicity. Latino ethnic background will be defined as a geographic, historical, and cultural heritage shared among persons from Spanish-speaking countries in South and Central America, Mexico, and the Caribbean. Both parents and all grandparents of the participant have to be Latino, with Spanish as the primary language. Participants have to be white; native aboriginal Indians, Asians, and blacks will be excluded. 2. Age greater than or equal to 18 years. 3. Documentation of hepatitis C infection by demonstration of a positive test for hepatitis C antibody and HCV RNA level of greater than or equal to 2,000 IU/mL. 4. Documentation of HIV-1 infection in the second group of co-infected participants by a licensed enzyme-linked immunosorbent assay and confirmed by a Western blot or by HIV polymerase chain reaction positive. 5. Participants with HIV: CD4+ cell counts greater than or equal to 100 cells/mm(3) or CD4+ cell percentage greater than or equal to 14%. 6. Ability to provide informed consent and willingness to comply with the study requirements, storage of blood samples and clinic policies. 7. Participants must have a primary care physician managing medical problems. 8. For HIV infected participants, care provided by a primary physician must be consistent with the current DHHS guidelines. For those on therapy, HAART will be provided by their physician. 9. Willing to undergo genetic testing 10. About to start HCV treatment (with or without direct acting agents DAAs) A subject will be ineligible to participate in this study if any of the following are met: 1. Unable to comply with research study visits 2. Have any condition that the investigator considers a contraindication to study participation. 3. Pregnant or breastfeeding women. 4. Patients with poor venous access | 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, Arthroplasty, Knee Replacement Replacement, Total Knee Total Knee Replacement Scheduled to undergo primary total knee arthroplasty Age 18 or over Inability to provide informed consent or to comply with study assessments due to cognitive impairment or geographic distance Age 17 or younger Allergies to chlorhexadine gluconate or povidone iodine Topical antimicrobial use within 14 days of surgery Any active dermatoses or open wounds over the operative site Any condition requiring antibiotics 14 days prior to arriving for surgery Patients with chronic immunosuppression (such as HIV/AIDS) Unable to adhere to follow up schedule and treatment | 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): 65.0-999.0, Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL) Key Histologically or cytologically confirmed CLL or SLL Age ≥ 65 Presence of measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥ 1.5 cm in the longest diameter (LD) and ≥ 1.0 cm in the longest perpendicular diameter (LPD) as assessed by physical exam, computed tomography (CT) or magnetic resonance imaging (MRI)) CLL Binet Stage C or Rai Stage III or IV or has active disease defined by meeting at least one of the following Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive (ie, > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly Massive nodes (ie, > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than 6 months Prior therapy for CLL or SLL, except corticosteroids for symptom relief Treatment with a short course of corticosteroids for symptom relief within 1-week prior to Visit 1 Known active central nervous system involvement of the malignancy Ongoing active, serious infection requiring systemic therapy. Patients may be receiving prophylactic antibiotics and antiviral therapy at the discretion of the treating physician Serum creatinine ≥ 2.0 mg/dL Serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) or serum transaminases (ie, aspartate aminotransferase (AST), alanine aminotransferase (ALT)) ≥ 2 x upper limit of normal Positive test for human immunodeficiency virus (HIV) antibodies Active hepatitis B or C (confirmed by ribonucleic acid (RNA) test). Patients with serologic evidence of prior exposure are eligible History of a non-CLL malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to study entry, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years. 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): 2.0-999.0, Leukemia Adult and pediatric (=/> 2 years old) patients with a diagnosis of acute myelogenous leukemia (including undifferentiated and bi-phenotypic leukemia), or high-risk myelodysplastic syndrome, or chronic myelogenous leukemia in blast crisis who will receive first or second anti-leukemia therapeutic intent with chemotherapy, targeted therapy or hypomethylating agents 2. Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital Patients with baseline (at start leukemia treatment) infection, defined as patients with a)fever and known positive cultures at the time of randomization; or b) chest or sinus computed tomography with findings suggestive of pneumonia or sinusitis; or c) one positive galactomannan test >/= 1 or two positive galactomannan text >/= 0.5 to 1 2. Patients with Zubrod performance status >/= 3 | 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 Hematopoietic/Lymphoid Cancer Prolymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Previously treated patients with a diagnosis of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or prolymphocytic leukemia (PLL) by NCI with intermediate or high risk B-Cell chronic lymphocytic leukemia (CLL)(Modified Rai stage) satisfying at least one of the for active disease requiring treatment;patients with a history of Richter's transformation are eligible if they now have evidence of chronic lymphocytic leukemia (CLL) only, with < 10% large cells in the bone marrow Massive or progressive splenomegaly and/or lymphadenopathy; or need for cytoreduction for stem cell transplant Anemia (hemoglobin < 11 g/dl) or thrombocytopenia (platelets < 100 x 10^9/L) Presence of weight loss > 10% over the preceding 6 month period NCI grade 2 or 3 fatigue Fevers > 100.5 °C or night sweats for greater than 2 weeks without evidence of infection Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months Creatinine Clearance (CrCl) > 15mL/min Alanine aminotransferase (ALT) < 3X upper limit of normal (ULN) Bilirubin =< 2 times the upper limit of normal, unless disease related Absence of previously treated chronic lymphocytic leukemia (CLL) Female subject that is pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception prior to study entry, duration of study participation,and 30 days following study completion; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women Patients with congestive heart failure (CHF)in whom pre-treatment hydration would be prohibitive;New York Heart Association (NYHA) Class III/IV CHF is excluded Patients who have had treatment for chronic lymphocytic leukemia (CLL) within 2 weeks, although palliative steroids are acceptable Patient unable to give written informed consent Failure to recover from toxicity of previous radiotherapy or chemotherapy to grade 1 Patients with active infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics or antivirals are acceptable Patients who have previously taken bortezomib | 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): 18.0-85.0, Mediastinal or Intra-abdominal Lymphadenopathy, Pancreatic Masses, Left Adrenal Masses, Gastrointestinal Submucosal Lesions, and Liver Masses Age greater than 18 years Presence of mediastinal or intra-abdominal lymphadenopathy, solid pancreatic mass, left adrenal mass, gastrointestinal submucosal lesions or liver mass confirmed by at least a single investigational modality CT scan, magnetic resonance imaging, endoscopy Capable of providing informed consent Severe coagulopathy (INR > 1.5) or thrombocytopenia (platelet count < 50,000) Lesion unable to be sampled due to the presence of intervening blood vessels Results of EUS-FNA would not impact patient management Inability to provide 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, B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Prolymphocyctic Leukemia Richter's Transformation Subjects with histologically confirmed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or Richter's transformation arising out of CLL/SLL as defined by WHO classification of hematopoietic neoplasms and satisfying ≥ 1 of the following conditions Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow involvement Presence of unintentional weight loss > 10% over the preceding 6 months NCI CTCAE Grade 2 or 3 fatigue Fevers > 100.5 degree or night sweats for > 2 weeks without evidence of infection Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months Need for cytoreduction prior to stem cell transplant 2. Subjects must have failed ≥ 2 prior therapies for CLL including a nucleoside analog or ≥ 2 prior therapies not including nucleoside analog if there is a contraindication to such therapy 3. 10% expression of CD20 on CLL/SLL cells 4. ECOG performance status ≤ 2 5. Life expectancy ≥ 12 weeks 6. Subjects must have organ and marrow function as defined below Absolute neutrophil count (ANC) ≥ 1000/µL in the absence of bone marrow involvement Platelets ≥ 30,000/μL in the absence of bone marrow involvement 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 PCI-32765 PO, or put the study outcomes at undue risk 2. Significant cardiovascular disease 3. Any condition which could interfere with the absorption or metabolism of PCI-32765 including unable to swallow capsules, 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 4. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection 5. Any anticancer immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug. Corticosteroids for disease-related symptoms are allowed provided 1 week washout occurs 6. Active central nervous system (CNS) involvement by lymphoma 7. Major surgery within 4 weeks before first dose of study drug 8. Lactating or pregnant 9. Known moderate to severe chronic obstructive pulmonary disease (COPD) 10. History of 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 at least 2 years or which will not limit survival to < 2 years 11. History of Grade ≥ 2 toxicity continuing from prior anticancer therapy including radiation | 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): 13.0-85.0, Myelodysplastic Syndrome (MDS) Aplastic Anaemia (AA) Myelofibrosis (MF) Thalassemia Intermedia A diagnosis of MDS, AA, MF or thal based on currently recognized diagnostic criteria. 2. Explored or undergone established therapies eg haemopoietic stem cell transplant, immunosuppressive therapy, chemotherapy, growth factors, thalidomide, hypomethylating agent or androgens, and (a) are deemed not suitable, or (b) refuse or (c) have failed therapy 3. A preceding follow up period (without or with treatment) of 2-4 months as baseline (depending on the severity of cytopenia) before being enrolled into this study 4. Understand the trial nature of this treatment, agree to be compliant to medication, do not self medicate and have signed informed consent 5. Agreeable to regular blood tests and follow up marrow study as listed in schedule Life expectancy of shorter than one year 2. Significant organ failure including the following 3. Renal impairment with Cr above 200umol/L 4. Liver impairment with serum bilirubin > 2x upper limits or transaminase >3x upper limits 5. Escalation of treatment of introduction of new agents including growth factors, thalidomide, hypomethylating agents, immunosuppressive therapy or androgens once started on treatment with TCM is not allowed. Continuation of current therapy at same or lower doses is allowed 6. Women during pregnancy or lactation | 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): 65.0-999.0, Lymphocytic Leukemia, Chronic Adult patients, >/= 65 years of age Previously untreated B-cell chronic lymphocytic leukemia (CLL) Binet stage C or active Binet stage A and B disease Prior treatment for CLL CLL with transformation (Richter's syndrome) Suspected or known central nervous system (CNS) involvement of CLL Impaired renal or hepatic function Human Immunodeficiency Virus (HIV) positivity, active hepatitis B/C or Hepatitis B Virus (HBV) surface antigen positive, or any active or uncontrolled infections Patients with anti-HBV core antibodies (past infection with HBV) but who are negative for Hepatitis B Virus Surface Antigen (HBVsAg) (either anti-HBS Ab positive or negative) and are positive for HBV Deoxyribonucleic acid (DNA) by Polymerase chain reaction (PCR) analysis Concomitant diseases requiring chronic steroid administration Active second malignancy within the 2 years prior to study (except for non-melanoma skin cancer and in situ cervix or breast or prostate carcinoma) Eastern Cooperative Oncology Group (ECOG) performance status >/= 3 | 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, Hepatitis C Male or female patients of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the study 2. HCV genotype 1 infected null responders to prior therapy comprised of pegylated interferon and ribavirin (standard of care, SOC) defined as Failure to achieve an early virologic response (< 2 log decline in HCV-RNA by Week 12), or If Week 12 HCV-RNA was not obtained, post Week 12 HCV-RNA response was < 2 log decline 3. Screening HCV-RNA viral load of > 5.0 log (i.e., >100,000 IU/mL) 4. alpha-fetoprotein (AFP) less than or equal to 100 ng/mL 5. Hemoglobin greater than or equal to 12 g/dL for women and greater than or equal to 13 g/dL for men, hemoglobin A1c less than or equal to 7.5 %, platelet count greater than or equal to 90 x 10^9/L, and white blood cell count greater than or equal to 1.5 x 10^9/L 6. Thyroid Stimulating Hormone (TSH) within normal limits 7. In the opinion of the Principal Investigator, the patient met the 80%/80%/80% rule during the previous pegylated interferon and ribavirin therapy (i.e., received at least 80% of the pegylated interferon and ribavirin doses, at least 80% of the dose size, for at least 80% of the treatment duration) 8. Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from screening to at least six months after the completion of the study < 2 log decline in HCV-RNA at Week 12 but > 2 log decline at any time from Week 12 to Week 24 during prior therapy with pegylated interferon and ribavirin (prior standard of care therapy) 2. Decompensated or severe liver disease defined by one or more of the following Prothrombin time 4 seconds > control or INR (international normalized ratio) > 1.2 Total bilirubin ≥ 1.5 mg/dL or direct bilirubin ≥ 1 mg/dL Serum albumin below normal limits aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 5 x upper limit of normal (ULN) at screening Presence of ascites 3. Hepatic encephalopathy 4. Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques) 5. Clinically significant ocular findings such as retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or other abnormality 6. Known history or presence of human immunodeficiency virus (HIV) infection 7. Co-infection with hepatitis B virus (HBV) 8. If female: pregnant, lactating, or positive serum or urine pregnancy test 9. Male partners of women who are currently pregnant 10. Renal impairment (creatinine > 1.2 x ULN), serum creatinine clearance < 50 mL/min, or hepatorenal syndrome with ascites 11. Hospitalization for liver disease within 60 days of screening 12. History of alcohol abuse (> 50 g per day) within the past year 13. History of severe psychiatric disease, especially depression, characterized by Suicide attempt Hospitalization for psychiatric disease Period of disability as a result of psychiatric disease 14. Prior exposure to CTS-1027 15. Patients who qualify as a null-responder based on treatment(s) other than pegylated interferon and ribavirin 16. History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose corrected Q-T interval (QTc) of > 450 milliseconds 17. History of or current autoimmune disease 18. Diagnosis of or symptoms suggestive of fibromyalgia 19. Currently on liver transplantation waiting list or recipient of any organ transplant 20. Other concomitant disease or condition likely to significantly decrease life expectancy (e.g., moderate to severe congestive heart failure) or any malignancy other than curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for five or more years 21. Exposure to any other investigational treatment for any aspect of disease associated with HCV during the past 6 months 22. Exposure to any investigational drug or device within 30 days of dosing, or scheduled receipt of another investigational drug or device during the course of 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): 18.0-999.0, Colorectal Cancer Patients with the diagnosis of metastatic colorectal cancer, either newly diagnosed or recurrent, with measurable disease that has not been irradiated within the last 5 weeks Age > 18 years old ECOG performance status 0-3 Patients who have received prior therapy in the last 5 weeks Ongoing therapy with a particular regimen that was initiated prior to enrollment and lack of availability of baseline CTC evaluation Patient with concurrent diagnosis of other active solid malignancies will be Patient life expectancy of less than six weeks | 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 Small Lymphocytic Lymphoma Histologically confirmed CLL or SLL and satisfying at least 1 of the following for requiring treatment Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow involvement Presence of unintentional weight loss > 10% over the preceding 6 months NCI CTCAE Grade 2 or 3 fatigue Fevers > 100.5° or night sweats for > 2 weeks without evidence of infection Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months 2. 1 to 3 prior treatment regimens for CLL/SLL 3. ECOG performance status of ≤ 1 4. ≥ 18 years of age 5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty 6. 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) Any chemotherapy, therapeutic antineoplastic antibodies (not including radio or toxin immunoconjugates), radiation therapy, or experimental antineoplastic therapy within 4 weeks of first dose of study drug 2. Radio or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug 3. Concomitant use of medicines known to cause QT prolongation or torsades de pointes 4. Transformed lymphoma or Richter's transformation Any 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 PCI-32765 PO, or put the study outcomes at undue risk 5. Any of the following laboratory abnormalities: oAbsolute neutrophil count (ANC) < 1000 cells/mm3 (1.0 x 109/L) oPlatelet count < 50,000/mm3 (50 x 109/L) oSerum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) oCreatinine > 2.0 x ULN or creatinine clearance < 40 mL/min | 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 B-cell Chronic Lymphocytic Leukemia (CLL) Patients must have intermediate or high-risk categories of the modified 3-stage Rai and Binet staging Patient MUST have progressive or symptomatic disease as defined by any of the following conditions Progressive lymphocytosis with a lymphocyte count increased > 50% over the last 2 months period or an anticipation of the doubling time in less than 6 months Progressive or symptomatic splenomegaly or hepatomegaly Progressive or symptomatic lymphadenopathy Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia Presence of any B-symptoms: weight loss ≥ 10% within the previous 6 months, fever > 38.0°C for ≥ 2 weeks without evidence of infection, or night sweats without evidence of infection Patient must have received one or more prior therapies for Chronic Lymphocytic Leukemia. Patients may have received any of the following prior treatment regimens: fludarabine-containing combinations, alemtuzumab single agent or combination, rituximab combinations, chlorambucil, cyclophosphamide +/ prednisone, or other forms of immunotherapy… Patients having received Valproic Acid (VPA) within 3 months Previous, suspected or known hypersensitivity to VPA, or any of its derivatives Liver porphyria Epilepsy due to mitochondrial diseases Ongoing treatment with VPA-interacting drugs Cumulative Illness rating Scale (CIRS) > 6 Prior allogenic or autologous bone marrow transplantation less than 12 months Patient having received any anticancer agents (chemotherapy, immunotherapy or targeted agents) within 4 weeks Central Nervous System involvement Concomitant disease requiring prolonged use of corticosteroids (> 1 month) | 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, Cytopenias Erythropenia (Diagnosis) Use of linezolid is not less than 3 days Serious adverse reactions | 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): 12.0-999.0, Leishmaniasis Cutaneous Leishmaniasis Gender: Male or female Age: >12 yrs of age Clinicla presentation: 1-2 ulcerative lesions, each < 30 mm in largest diameter, and with a total lesion area <900 mm2 Parasitological confirmation of the lesion will be made by visualization or culture of leishmania from the biopsy or aspirate of the lesion Previous treatment for leishmaniasis: therapy with Sb, pentamidine, amphotericin B, miltefosine, imidazoles or allopurinol in the last 3 months Concomitant diseases by history that would be likely in the PI's opinion to interact, either positively or negatively, with IL Sb treatment | 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, Myelodysplastic Syndrome MDS defined according to WHO classification (also including RAEB-T according to FAB classification) (see appendix 1) with intermediate-2 or high risk IPSS (see appendix 1) Age ≥ 18 years and <75 years Must understand and voluntarily sign an informed consent form Must be able to adhere to the study visit schedule and other protocol requirements Patients must have ECOG performance status (PS) of 0 and no major comorbidities preventing administration of an intensified regimen of azacitidine Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must Have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. Lactating patients are excluded Agree to use, and to be able to comply with, effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy Male patients must Patients with a history of myeloproliferative syndrome or CMML Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C Pregnant and lactating patients are excluded because the effects of azacitidine on a fetus or a breast-fed child are unknown Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA > II), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients receiving any other standard or investigational cytotoxic treatment for their hematologic malignancy in the last 8 weeks Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities of an intensified regimen of azacitidine Less than 6 months since prior allogeneic bone marrow transplantation Less than 3 months since prior autologous bone marrow or stem cell transplantation Active cancer or prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥ 3 years Prior treatment with azacitidine | 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, Leukaemia Adults with documented diagnosis of active CLL requiring treatment Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm Must be refractory to fludarabine treatment Age 18 yrs or older At least 2 prior therapies for CLL Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Signed written informed consent Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment Human immunodeficiency virus (HIV) positive Significant concurrent, uncontrolled medical condition Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of 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, Chronic Myelogenous Leukemia Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Hodgkins Lymphoma Non-Hodgkins Lymphoma Individuals who are candidates for allotransplant therapy for hematologic malignancies and are being evaluated at the Clinical Center for planned allotransplantation. 2. Individuals who have received allotransplant treatment for hematologic malignancy and have: 1. Hematologic recovery after allotransplant: e.g., have had neutrophil recovery to 500 cells/mcL. Secondary cytopenias or cytopenias due to disease progression will be permitted. Note: this requirement will not apply to subjects enrolling pre-transplant, i.e, who receive transplant-related medical care at the Clinical Center (CC). 2. An ongoing relationship with a primary oncologist who will continue to provide continuity of care during and after study participation. 3. Following record review and information exchange between the patients primary oncologist and the National Cancer Institute (NCI) Principal Investigator (PI)/Designee, the PI/Designee determines that the individual reasonably could be expected to safely tolerate travel to and from the Clinical Center (CC) to undergo evaluation as defined in the protocol, in the event that the patient is ineligible or uninterested in participating in open treatment protocols. 3. 18-99 years. 4. Ability of subject to understand and the willingness to sign a written informed consent document. DONOR 1. Individuals who are/will be the donors of allogeneic hematopoietic stem cell transplants received by Recipient-Subjects who are to be enrolled on this protocol. 2. Age 18-99 years. 3. Ability of the subject to understand and the willingness to sign a written informed consent document. 4. Individuals with evidence of infection with transfusion-transmittable agents (Hepatitis B and C Viruses (HBV, HCV); Human Immunodeficiency Virus (HIV (Omega)), Human TLymphotrophic Virus (HTLV I/II), West Nile Virus (WNV) and Trypanosoma cruzi) will not be excluded from study participation. However, Donor-Subjects with evidence of HIV infection will only be able to donate cells for research. Donors with a history of HBV or HCV infection will be able to donate for research, and may be eligible to donate for therapeutic administration. However, determination of permissibility for clinical donation will require a hepatology consultation and the consent of the intended recipient after discussion of the risk/benefit of the donor cell product and the possibility/consequences of transmission. The PI/Designee will make the final determination of permissibility of donation for recipient cell therapy. 6. Unrelated donor selection will be in accordance with the National Marrow Donor Program (NMDP) standards. When a potentially eligible recipient of an unrelated donor product from an NMDP Center is identified, the recipient will complete an NMDP search transfer request to allow NIH NMDP staff to contact the NMDP Coordinating Center, who will, in turn, contact the donors prior Donor Center. The NMDP Policy for Subsequent Donation Requests will be followed and the appropriate forms (Subsequent Donation Request Form and Therapeutic T Cell Collection Prescription Form) will be submitted as required Individuals with rapid disease progression or aggressive cancer histology who, in the opinion of the PI/Designee, require urgent therapy within 30 days in order to preserve organ function or quality of life. This restriction will not apply if there is no approved therapy with a reasonable chance of disease response, if the patient does not have access to an effective therapy and the patient appears to be eligible for an accruing CC treatment protocol or if the patient is enrolled on an NIH/CC clinical protocol, e.g., allotransplant protocol. 2. Pregnancy or lactating. Additionally, Recipient-Subjects of childbearing potential that will receive cancer treatment under this protocol must be willing to use an effective method of contraception. DONOR 1. Adult donors who are not eligible for clinical donation will not be excluded from study participation, but will only be able to donate cells for research | 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, Hodgkin Lymphoma Age range: 18-65 years old Histological confirmed refractory or relapsed Hodgkin lymphoma With at least one site of measurable disease according to IWC ECOG performance status 0-1 Life expectancy of more than 3 months Bone marrow function: ANC≧1.5×109/L, PLT≧100×109/L, Hb≧80g/L Liver function: total bilirubin, ALT and AST <1.5×UNL Renal function: Cr<1.5×UNL, CCR≧45ml/min No contraindication for transplantation No prior chemotherapy With more than 2 lines of prior chemotherapy exposure Evidence of CNS and bone marrow involvement History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix Pregnant or lactating women Significant active infection | 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, Chronic Lymphocytic Leukemia diagnosis of CLL at least two available stored samples at least one criterium not fulfilled | 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, Lymphoma Male or Female, aged ≥ 18 yrs ECOG performance score of 0, 1 or 2 Life expectancy of at least 12 weeks Haematological and biochemical indices within the ranges shown below Lab Test Value required Haemoglobin (Hb) ≥ 9g/dL White Blood Count (WBC) ≥ 2x109/L Platelet count ≥ 100x109/L Absolute Neutrophil count ≥ 1.0x109/L; Serum bilirubin ≤ 1.5 x ULN AST (SGOT) or ALT ≤ 1.5 x ULN Creatinine clearance (Cockcroft-Gault) > 50 ml/min Relapsed or refractory DLBCL in which all participants must have received at least one potentially curative established immunochemotherapy lymphoma regimen that contained rituximab (e.g. R-CHOP, R-PMitCEBO, R-GCVP, R-CNOP). Participants must also have failed or be ineligible for salvage/high dose therapy Relapsed or refractory DLBCL proven by biopsy (within 6 months of enrolment in trial); either de novo DLBCL or transformed follicular lymphoma At least 1 lesion (> 1.5cm), not previously irradiated, that can be accurately measured on CT and which is FDG avid on CT-PET scanning, as defined by Cheson criteria Able to give informed consent and capable of co-operating with protocol Any anti-cancer therapy (including radiotherapy and participation in other clinical trials) within 28 days prior to Day 1. Patients may however be receiving corticosteroids as an anti-lymphoma treatment of 50mg daily prednisolone or equivalent up until screening. At screening (or before) this must be tapered down so that they are only on a low dose (10mg daily or less) by the time AZD1152 commences. This may be continued for indications other than lymphoma treatment throughout the study Any unresolved toxicity from prior anti-cancer therapy greater than CTCAE grade I (except alopecia) Previous treatment with aurora kinase inhibitors Clinical evidence of central nervous system involvement Another active malignancy within the past five years, except adequately treated basal or squamous cell carcinoma of the skin, or carcinoma of the cervix in situ Clinically significant and uncontrolled major medical condition(s) including but not limited to: active infection, bleeding diathesis, symptomatic congestive heart failure, cardiac arrhythmia or psychiatric illness/social situations which would limit compliance with protocol requirements Major surgery within 4 weeks prior to entry into the study (excluding placement of vascular access or biopsy) that involved general anaesthesia or respiratory assistance Mean QTc interval > 470 ms calculated from 3 ECGs using Fridericia's or Bazett's correction on 12-lead ECG machine Serologically positive for HIV, hepatitis B or C assessed within 28 days of initiation of study treatment using an ELISA method performed by an HPA accredited laboratory Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study (both male and female participants) | 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 Age older than 18 years 2. Patient with suspected malignant mediastinal lymphadenopathy Age younger than 18 years 2. Bleeding diathesis(INR > 1.4, Platelet count < 10,000/mcl) | 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): 12.0-75.0, Cutaneous Leishmaniasis Parasitological confirmation at least 1 lesion must be ulcerative No specific antileishmanial therapy during the previous six months Concomitant diseases such as Tuberculosis, HIV, diabetes, renal failure, liver disease abnormalities CTC 2 in blood, liver, kidney test or EKG | 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): 12.0-999.0, Cutaneous Leishmaniasis Gender: Male or female Age: >12 yrs of age Presentation: At least 1 lesion must be ulcerative. No more than 3 lesions. Parasitology: Parasitological confirmation of 1 lesion will be made by visualization or culture of leishmania from the biopsy or aspirate of the lesion No specific or putatively specific therapy (Sb, pentamidine, amphotericin B, imidazoles, allopurinol) in the last 6 months Previous treatment for leishmaniasis concomitant diseases by history abnormal complete blood counts (white blood count, hemoglobin, platelet count), values of liver transaminases (SGOT), kidney function tests (creatinine) pregnancy or breastfeeding or not willing to take contraception for 3 months after the end of treatment | 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 Thrombocytopenia Confirmed diagnosis of CLL (based immunophenotyping performed at the central reference laboratory of the in Cologne) Platelet count <50 000/μl at time of screening (measured and confirmed twice) Patient is planned to receive alkylating agents and/or fludarabine-based therapy as 2nd or higher-line treatment ECOG Performance Status of 0-2 Age >= 18 years Signed written informed consent, according to ICH-GCP, and national/local regulation, prior to performing any study-specific procedures Negative pregnancy test and willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly) Able to understand and comply with protocol requirements and instructions and intend to complete the study as planned Adequate renal function (creatinine must not exceed the upper limit of normal (ULN) reference range by more than 50%) at study entry Adequate liver function: bilirubin £ 1.5 times the upper limit of normal. ALT or AST <= 3 times the upper limit of normal without liver involvement with CLL and <= 5 times the upper limit of normal in case of the liver involvement with CLL Thrombocytopenia that is primarily caused by ITP Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of last fludarabine and/or bendamustine based therapy. NOTE: Subjects refractory to rituximab monotherapy as last therapy are permitted No prior therapy for CLL Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy >100mg equivalent to hydrocortisone, or chemotherapy Platelet count > 50 000/μl at screening Richter's transformation CNS involvement of B-CLL Active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment Past or current malignancy other than CLL (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless tumor was successfully treated with curative intent at least 2 years prior to trial entry Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months, congestive heart failure, etc | 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): 15.0-85.0, CLL Patients with CLL and lymphocyte count > 10 x 109/l Acute infection | 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, Lymphocytic Leukemia, Chronic Confirmed diagnosis of CD20-positive B-cell CLL (per International Workshop on Chronic Lymphocytic Leukemia [IWCLL] guidelines) Rai Stage III/IV or Binet Stage C disease, or Rai Stage I/II or Binet Stage B disease that requires treatment according to IWCLL guidelines No previous treatment for CLL chemotherapy, radiotherapy or immunotherapy; no previous rituximab treatment for autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP); prior use of steroids for AIHA or ITP is allowed Eastern Cooperative Oncology Group performance status of 0, 1 or 2 Confirmed diagnosis of Transformation of CLL to aggressive B-cell malignancy History of severe allergic or anaphylactic reactions to monoclonal antibody therapy Evidence of severe, uncontrolled concomitant disease Known active infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks before the start of Cycle 1 Seropositive for human immunodeficiency virus (HIV) Positive for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology) Positive for hepatitis C (hepatitis C virus [HCV] antibody serology testing) Pregnant or lactating women Concurrent (or within 7 days prior to first dose of study treatment) systemic corticosteroid use, except for low-dose corticosteroid therapy used to treat chronic medical conditions | 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, Pancreatic Cancer years of age or older Diagnosis of metastatic pancreatic cancer; subjects must have had measurable, or evaluable disease that was histologically confirmed Karnofsky performance status of ≥ 60 Subjects must have failed 1st-line gemcitabine treatment for metastatic pancreatic cancer: o An alternate chemotherapeutic agent was an acceptable substitute as 1st-line therapy in the event that the subject was intolerant to or ineligible to receive gemcitabine ≥ 2 weeks elapsed from the completion of previous chemotherapy, and subjects must have recovered or been at new stable baseline from any related toxicities More than 1 prior chemotherapy regimen (not including adjuvant therapy) for metastatic disease Evidence of central nervous system (CNS) metastases (unless stable for > 3 months) or history of uncontrolled seizures Ongoing radiation therapy or prior radiation therapy administered as a second-line treatment Other active malignancy except basal or squamous carcinoma of the skin Inability to swallow food or any condition of the upper GI tract that precluded administration of oral medications Inadequate renal, hepatic and bone marrow function demonstrated by clinical observations and/or laboratory assessments | 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, Lymphoma Histologically confirmed OAML Non-conjunctival or bilateral conjunctival (TNM-based, above T1N0M0 or bT1N0M0), Ann Arbor stage I and II OAML Previously untreated Age ≥18 years Performance status: ECOG 0-2 Adequate hematological function: hemoglobin ≥9 g/dL,, absolute neutrophil count (ANC) ≥1,500/μL, and platelet count ≥100,000/μL, unless abnormalities are due to bone marrow involvement by the lymphoma Adequate liver function tests: i. Transaminase (AST/ALT) <3 times the upper normal value ii. Bilirubin <2 times the upper normal value Adequate renal function:serum creatinine level <2 mg/dL (177 μmol/L) Life expectancy ≥ 6 months A negative serum or urine pregnancy test before treatment must be available for both premenopausal women and for women who have <2 years after the onset of menopause NHL subtypes other than OAML Primary conjunctival OAML, unilateral involved (T1N0M0) Ann Arbor stage III or IV CNS involvement by the lymphoma or any evidence of spinal cord compression. Brain CT/MRI is only mandatory (within 4 weeks) with clinical suspicion of CNS involvement by the lymphoma Pregnant or lactating women, women of child-bearing potential not using adequate contraception Inadequate liver function tests: i. Transaminase (AST/ALT) ≥3 times the upper normal value or ii. Bilirubin ≥2 times the upper normal value Inadequate renal function: i. serum creatinine level <2 mg/dL (177 μmol/L) Other serious illness or medical conditions i. Unstable cardiac disease despite treatment; myocardial infarction within 6 months prior to study entry ii. History of significant neurological or psychiatric disorders including dementia or seizures Active uncontrolled infection (HIV, hepatitis B, Hepatitis C, active Tuberculosis, active bacterial, or active fungal infection) Any other malignancies within the past 5 years except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri | 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 Leukaemia Small Lymphocytic Lymphoma Aged ≥ 18 years Patients affected by CLL / SLL Presence of active disease defined as the presence of one of the following: Disease related symptoms (weight loss >10% in the last 6 months, fever >38° C for 2 weeks without evidence of infection, or marked asthenia, or profuse sweating without evidence of infection) Massive nodes (at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy Massive (at least 6 cm below left costal margin) or progressive or symptomatic splenomegaly Progressive lymphocytosis (increased >50% in 2 months) or lymphocyte doubling time < 6 months Evidence of progressive bone marrow insufficiency seen as evidence of or worsening of anemia and or thrombocytopenia Autoimmune anemia and or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy Age < 18 years Patients with cardiac, pulmonary, neurological, psychiatric or serious metabolic conditions not related to CLL / SLL Altered hepatic function (bilirubin, GOT, GPT, or gammaGT > 2 times upper limit of normal) not attributable to CLL / SLL Altered renal function (creatinine > 1,5 times upper limit of normal) Patients with serious active infections Pregnancy and/ or breastfeeding Patients with positive serology for HBSAG or HBCAB without evaluation by a hepatologist Patients with positive serology for HIV Life expectancy of less than 12 months Not taking any other experimental drugs | 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, Leukaemia, Lymphocytic, Chronic All CLL patients who have previously received Arzerra, whether alive or deceased Patients who have either completed the full course of Arzerra therapy or discontinued treatment early CLL patients newly initiating Arzerra Patients having been treated with Arzerra in phase II or phase III clinical trials | 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 Documented CLL/SLL deletion by FISH in 20% or more nuclei on peripheral blood, bone marrow or lymph node Normal organ function Pregnant or breast feeding Current active hepatic or biliary disease Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, tuberculosis and active Hepatitis C History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae Other past or current malignancy. Participants who have been free of malignancy for at least 2 years, or who have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible Known HIV positive Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to study entry, congestive heart failure, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities Significant concurrent uncontrolled medical conditions including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the subject Positive serology for Hepatitis B or C History of allergic reactions attributed to ofatumumab | 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, Leukemia Leukemia, Lymphocytyc CLL (Chronic Lymphocytic Leukemia) SLL (Small Lymphocytic Lymphoma) Cohort 1: Treated and untreated patients age 65 or older and need for therapy Cohort 2: Treated (maximum accrual n=16) and untreated (n=27, evaluable) patients at least 18 years old with 17p deletion or p53 expression by immunohistochemistry or p53 mutation by sequencing analysis. 2. Men and women with histologically confirmed disease as defined by the following B-lymphocytosis greater than 5000 cells/microL (may be less than 5000 cells/microL if lymphadenopathy is present with histologic confirmation of lymph node involvement by SLL) Immunophenotypic profile 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 no t11;14 translocation present. 3. Active disease as defined by at least one of the following Weight loss greater than or equal to 10% within the previous 6 months Extreme fatigue Fevers of greater than 100.5 degrees 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 Massive nodes or clusters or progressive lymphadenopathy Previous radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product fpr CCL treatement in the last 4 weeks (i.e. intravenous immunoglobulin). 2. Transformed CLL 3. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy 4. Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper limit of normal unless dute to Gilbert's disease, AST/ ALT greater than or equal to 2.5 times institutional upper limit of normal unless due to infiltration of the liver. 5. Impaired renal funtion: Creatinine greater than or equal to 2.0 mg/dL or GFR less than or equal to 50ml/min 6. 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 PCI-32765 PO, or put the study outcomes at undue risk 7. Concomitant immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone > 20 mg/day), or experimental therapy 8. Active Hepatitis B infection 9. HIV infection 10. Female patients: Current pregnancy or unwilling to take oral contraceptives 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 yrs old 14. Known hypersensitivity to any component of PCI-32765 15. Any prior therapy with PCI 32765 or any other BTK inhibitors. 16. Requires anticoagulation with warfarin. 17. Requires treatment with strong CY3A4/5 and/or CYP2D6 inhibitors (unless no alternative is available) | 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): 18.0-45.0, Healthy Is the individual a healthy, normal adult man or woman who volunteers to participate? Is s/he within 18 to 45 years of age, inclusive? Is his/her BMI between 19 and 30 inclusive? Is she willing to avoid pregnancy by abstaining from sexual intercourse with a non-sterile male partner, or by the use one of the following methods: diaphragm + spermicide or condom + spermicide (at least 14 days before dosing), intra-uterine contraceptive device or hormonal contraceptives (at least 4 week prior to dosing) or has she been surgically sterile or post-menopausal at least six months prior to entering into the study? Is s/he considered reliable and capable of understanding his/her responsibility and role in the study? Has s/he provided written informed consent? Does the individual have a history or allergy or hypersensitivity to desloratadine? Does s/he have clinically significant laboratory abnormalities that would interfere with the conduct or interpretation of the study or jeopardize his/her safety? Does s/he have significant history or clinical evidence of auto-immune, cardiovascular, gastrointestinal, hematological, hematopoietic, hepatic, neurological, ongoing infection, pancreatic, or renal disease that would interfere with the conduct or interpretation of the study or jeopardize his/her safety? Is she nursing? Does s/he have serious psychological illness? Does s/he have significant history (within the past year) or clinical evidence of alcohol or drug abuse? Does s/he have a positive urine drug screen or a positive HIV-I, or hepatitis B or C screen, or a positive pregnancy test? Is s/he unable to refrain from the use of alcohol or xanthine-containing foods or beverages during periods beginning 48 hours prior to study drug administration and ending when the last blood sample has been taken in each study period? Has s/he used any prescription drug, other than hormonal contraceptives, during the 14 day period prior to study initiation, or any OTC drug during the 72 hour period preceding study initiation? Is s/he unable to refrain from the use of all concomitant medications, other than hormonal contraceptives, during 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, Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Patients must have histologically confirmed B-cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) or a B-cell prolymphocytic leukemia (B-PLL) according to 2008 World Health Organization (WHO) diagnostic Patients must meet one or more of the following modified indications for treatment as described in the 2008 International Workshop on chronic lymphocytic leukemia (CLL) (IWCLL) guidelines for the diagnosis and treatment of CLL Progressive disease or marked splenomegaly and/or lymphadenopathy or disease requiring de-bulking for future allogeneic transplantation Anemia (hemoglobin < 11 mg/dL) or thrombocytopenia (platelets < 100,000/μL) Unexplained weight loss exceeding 10% of body weight over the preceding 6 months Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology for Adverse Events (CTCAE) grade 2 or 3 fatigue Fevers > 100.5 º F or night sweats for greater than 2 weeks without evidence of infection Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of less than 6 months Need for cytoreduction prior to allogeneic stem cell transplant Patients must have received at least one prior therapy that includes either fludarabine or equivalent nucleoside analogue, or an alternative regimen if there was a contraindication (i.e. autoimmune hemolytic anemia) or patient elected not to receive fludarabine Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; corticosteroids alone will not be considered prior therapy, but must be discontinued at least 24 hours prior to the first day of therapy unless continued for indications other than the primary malignancy Patients who are receiving any other investigational agents Patients who have received prior treatment with dinaciclib will not be eligible; patients previously treated with ofatumumab will be eligible as long as their disease responded to previous treatment (defined as achieving at least stable disease by consensus criteria) and did not subsequently progress < 3 months from completing treatment Patients with known brain metastases should be excluded from this clinical trial History of allergic reactions attributed to compounds of similar chemical or biologic composition as dinaciclib History of anaphylactic reaction to rituximab or other anti-cluster of differentiation (CD)20 monoclonal antibody Because dinaciclib is metabolized by the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme, the of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications; any identified agent needs to be stopped at least 2 weeks prior to study registration; use of aprepitant will be permitted, however, based on drug-drug interaction study performed by the manufacturer showing no effect on dinaciclib pharmacokinetics (PK) Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are excluded 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 Pregnant and/or breast-feeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dinaciclib | 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): 7.0-100.0, Eosinophilia Hypereosinophilic Syndrome Leukocyte Disorder Hematologic Diseases Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following apply: 1. Subjects must be 7 years of age or older to enroll 2. Subject meets diagnostic for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia) 3. AEC greater than 1500 microL obtained within 14 days prior to enrollment 4. Willingness to perform the timed steroid challenge 5. Appropriate candidate for GC treatment after challenge 6. Willingness to have samples stored for future research A subject will not be eligible to participate in the study if any of the following apply: 1. Receiving >10 mg prednisone or equivalent at the time of enrollment. 2. Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be excluded). 3. AEC less than or equal to 1500/microl on the day of the steroid challenge 4. Use of immunomodulatory medications, (other than less than or equal to 10 mg/day prednisone) including but not limited to biologics, within the past 6 months. 5. Pregnant at the time of screening. 6. Have a known mutation in the FIP1L1-PDGFR gene. 7. Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol. 8. Weight less than 48 kg (106 lbs) in subjects less than 18 years of age | 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, Waldenström Macroglobulinemia Diagnosis of Waldenstrom Macroglobulinemia and presence of cluster of differentiation (CD)20+ tumor cells as determined by immune-histochemistry or flow cytometric analysis in bone marrow or representative lymphoid tissue specimen; to be deemed eligible, patients must meet at least one of the following Rising immunoglobulin (Ig)M Hemoglobin =< 10 g/dL Platelet count =< 100 x 10^9/L Symptomatic or bulky lymphadenopathy or organomegaly Systemic manifestations of Waldenstrom Macroglobulinemia (WM), such as hyperviscosity symptoms (patients with symptoms of hyperviscosity syndrome must be treated with plasmapheresis to control the syndrome prior to enrollment), neuropathy, amyloidosis, cryoglobulinemia, B-symptoms, or recurrent bleeding Must have a measurable disease as defined by the monoclonal IgM level of 1 g/dL on serum protein electrophoresis (SPEP); if the level of IgM on SPEP is less than 1 g/dL in patients who meet any in 2, then the IgM level obtained from nephelometric measurement may be used to justify this criterion Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2 Have a life expectancy of >= 3 months Absolute neutrophil count >= 1.0 x 10^9/L unless the result of disease infiltration of bone marrow Pregnant and nursing female patients Prior anti-neoplastic therapy for WM; the use of plasmapheresis to manage the symptoms of hyperviscosity and other IgM paraprotein mediated symptoms is allowed and does not disqualify a patient from the study; if a patient undergoes plasmapheresis within 8 weeks of starting the study treatment then the IgM level prior to plasmapheresis should be used for response assessment; neoplastic use of glucocorticoids is prohibited during the screening and treatment period; patients with active hyperviscosity symptoms should not be enrolled in this study unless the symptoms resolve after plasmapheresis Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug Received an investigational agent within 30 days prior to enrollment Known human immunodeficiency virus (HIV) positive Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if HBsAg is negative and hepatitis B core antibody (HBcAb) is positive, regardless of hepatitis B surface antibody (HBsAb) status, a HB deoxyribonucleic acid test will be performed and if HB DNA is positive the patient will be excluded; if a patient is HBsAg negative, HBcAb positive, and HBsAb positive, indicating past but not active infection, the patient will be included on the study Positive serology for hepatitis C (HC) defined as a positive test for Hep C by enzyme immunoassays (EIA), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result Diagnosis of a malignant disorder other than WM within 3 years of the study enrollment with the exception of completely resected non-melanoma skin cancer and successfully treated in-situ cancer Uncontrolled infection | 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 Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy Require therapy for CLL Have experienced CLL progression < 24 months since the completion of the last prior therapy Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities | 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): 18.0-65.0, Fibromyalgia In order to qualify the subject: 1. must have been diagnosed with fibromyalgia by a medical doctor 2. must be between the ages of 18 to 65 years of age 3. must have a weekly overall body pain average score ≥ 4 4. must pass a screening questionnaire that calculates a physical impairment of ≥ 10 5. must be on stable doses of his/her current medication for at least past four weeks 6. must limit any changes in his/her medication(s) (e.g., dose change, addition or discontinuation of any medication that effects the central nervous system, e.g., benzodiazepines, sedative/hypnotic, etc. ) during the 10-week study period unless medically necessary 7. must report all medication including herbal supplements and over-the-counter medications, e.g. cold medication, eye drops, etc. that he/she is currently taking to a member of the research team 8. must be willing to maintain a medication diary provided to him/her during the 10-week study period 9. must be willing to abstain (not take) any fibromyalgia related medication including over-the-counter for at least 8-hours prior to each of the two testing visits (Otherwise, he/she may take these medication(s) immediately after pain sensitivity testing has been completed and as prescribed in-between visits) 10. must agree to use a proven method of contraception to prevent pregnancy throughout this study The subject will not be allowed to participate if: 1. he/she has a history of seizures 2. he/she has atopic dermatitis (also called eczema) or chronic urticaria (hives) 3. he/she has chronic thrombocytopenia (a low blood platelet count) 4. she is currently pregnant, are planning to become pregnant, or is breastfeeding 5. he/she has been diagnosed by a psychiatrist with Schizophrenia or bipolar disorder 6. he/she has been diagnosed with another major rheumatic conditions (i.e. rheumatoid arthritis, systemic lupus erythematosus, scleroderma and/or other connective tissue diseases) 7. he/she plans to undergo an elective surgery within the study timeline 8. he/she is in the process of filing, or plan to file for disability benefits within the study timeline 9. his/her screening labs results are abnormal (i.e., elevated SGPT and low platelet count) 10. he/she is currently using any anti-allergy drugs (ophthalmic or oral histamine antagonist), leukotriene inhibitors (e.g., montelukast) or prednisone | 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, Hodgkin's Disease Non-Hodgkin's Lymphoma Lymphoproliferative Disease Lymphoma at time of Procurement 1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, (regardless of the histological subtype) or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV) who may subsequently be eligible for the treatment component 2. EBV positive tumor (can be pending at this time) 3. Weighs at least 12kg 4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. at time of Infusion 1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma (regardless of histologic subtype), or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV)* and In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse)** OR any patient with primary disease or in first remission 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 A) OR In remission or with minimal residual disease status after autologous or syngeneic SCT. (Group B) 2. EBV positive tumor 3. Patients with life expectancy greater than or equal 6 weeks. 4. Patients with bilirubin less than or equal to 3x upper limit of normal, AST less than or equal 5x upper limit of normal, and hemoglobin greater than or equal to 7.0 (may be a transfused value). 5. Patients with a creatinine less than or equal to 2x upper limit of normal for age 6. Pulse oximetry of > 90% on room air 7. Patients should have been off other investigational therapy for 4 weeks prior to entry in this study. PD1/PDL inhibitors will be allowed if medically indicated. 8. Patients with a Karnofsky/Lansky score of greater than or equal to 50 9. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom. 10. Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given copy of informed consent 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 Patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant at Time of Procurement 1. Active infection with HIV, HTLV, HBV, HCV (can be pending at this time) at Time of Infusion 1. Pregnant or lactating 2. Severe intercurrent infection. 3. Current use of systemic corticosteroids > 0.5 mg/kg/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): 18.0-999.0, B-Cell Chronic Lymphocytic Leukemia The diagnosis of CD20 positive chronic B lymphocytic leukemia (BCLL) confirmed by biopsy or flow-cytometry Previously treated patients with stage Rai I-IV and progressive disease (according to IWCLL 2008 guidelines). Active B-CLL is defined by at least one of the following: At least one of the disease related symptoms Constitutional symptoms Weight loss >10% within the previous 6 months Fatigue (e.g., WHO performance status >/=2) Fever >/=38C >/=2 weeks without evidence of infection Night sweats for more than 1 month without evidence of infection Evidence of progressive marrow failure as manifested by development of, or worsening of, anemia and/or thrombocytopenia Autoimmune hemolysis and/or thrombocytopenia poorly responsive to corticosteroid therapy Massive (i.e., >/=6 cm bellow left costal margin) or progressive or symptomatic splenomegaly Intolerance to exogenous protein or known severe reaction to the administration of Rituximab Active infection Cancer radiotherapy, biological therapy or chemotherapy within 3 weeks prior to Study Day 1 TBC or fungal infection within the past 6 months even if adequately controlled by treatment Severe organ deficiency preventing the participation in the study Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1 Active peptic ulcer Inadequately controlled diabetes mellitus Suspected or confirmed B-CLL CNS disease Known to be HIV positive | 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): 18.0-79.0, Lymphoma, Follicular Lymphoma, Non-Hodgkin Multiple Myleoma Lympocytic, Follicular Leukemia Hodgkin Lymphoma Eligible cases will be patients at a participating hospital who are between 18 and 79 years of age at time of initial diagnosis and admitted or treated with incident diagnoses of any lymphoid or myeloid neoplasm including all NHL and Hodgkin disease. Although it is important to understand the etiology of lymphoma in children as well, this undertaking would require additional hospitals, instruments, expertise, and funding that are not currently available to our research team. Adults over the age of 80 are generally among the sickest patients in the hospital and often have multiple comorbidities, which may preclude their participation in an interview of this length. Cases will be permanent residents of the general geographic region that is served by the hospital at the time of diagnosis. Cases will chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenstrom macroglobulinemia, plasmacytoma, multiple myeloma, aggressive NK cell leukemia, cutaneous lymphomas, myeloid neoplasms, and immunosuppression-associated cases (such as HIV, post transplant, Methotrexate use). 2,400 lymphoid neoplasm cases will be enrolled with less common subtypes in Asian populations including Hodgkin disease, multiple myeloma, chronic lymphocytic leukemia, and NK/T, T, follicular and marginal zone lymphoma, in order to increase statistical power to study risk factors for these tumors Cases with previous diagnosis of lymphoma, such as acute lymphoblastic lymphoma, multiple myeloma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, are ineligible | 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, Waldenstrom's Macroglobulinaemia Age ≥ 18 years Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein Previously untreated disease at any stage requiring therapy at the discretion of the treating physician. Suggested for initiating treatment haematological suppression to Hb <10 g/dl, or neutrophils <1.5x109/l or platelets <150x109/l clinical evidence of hyperviscosity bulky lymphadenopathy and/or bulky splenomegaly presence of B symptoms No previous chemotherapy (prior plasma exchange and steroids are permissible) Performance status grade 0 Life expectancy of greater than 6 months Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein Severe pre-existing neuropathy (> grade 2) Autoimmune cytopenias Evidence of active Hepatitis B or C infection (patients with evidence of past HepB infection may be eligible see appendix 6) Serological positivity for HIV Pregnant or lactating women Life expectancy severely limited by other illness Renal failure (creatinine clearance <30 ml/min) Severe impairment of liver function: alkaline phosphatase/bilirubin >2.5 times upper limit of normal (ULN), ALT/AST >2.5 times ULN not related to lymphoma (patients with Gilbert syndrome 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): 18.0-64.0, HIV Dementia Men and women 18 years of age or older and less than 65 years of age. Able to read and understand English. HIV infected on stable ART regimen for 5 months or greater, and not likely to change regimen for the duration of the study. Significant dementia but able to give consent (International HIV Dementia Scale score <10). Significant cognitive slowing on screening, defined as 1 SD below normal (t-score >60) on the Conner's CPT-II reaction time test. Beck Depression Inventory score <16. Documented HIV-1 RNA PCR <50 copies/mL and documented CD4 count >200 within 3 months of entry visit. Baseline CBC and chemistry panel Grade 1 or normal. For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within 24 months prior to study entry), or women who have not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy or tubal ligation) will require a negative serum or urine pregnancy test within 48 hours prior to entry. NOTE: Subject reported history is considered acceptable documentation of hysterectomy, bilateral oophorectomy, tubal ligation, tubal micro-inserts, menopause, and vasectomy/azoospermia. All subjects must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable methods of contraception, (condoms, without a spermicidal agent; a diaphragm or cervical cap without spermicide; an IUD; or hormone-based contraceptive), for 2 weeks before study treatment, while receiving study treatment, and for 6 weeks after receiving study treatment. Ability and willingness of subject to provide informed consent Inability to give informed consent. No proxy consent allowed. Uncontrolled hypertension (SBP >140 and DBP >90 at screening and baseline). Untreated hypogonadism, hypothyroidism or hyperthyroidism. Initiation of antidepressants, thyroid medication or anabolic steroids within 6 weeks of screening visit. Pregnancy or breast feeding. Clinically significant EKG abnormalities at screening. History of coronary artery disease, atherosclerotic disease, left ventricular hypertrophy, cardiomegaly, syncope, congestive heart failure, myocardial infarction, pacemaker, clinically significant arrhythmia, angina, history of treatment for arrhythmia. Brain related opportunistic infections, stroke, intracranial lesions/disease, or meningitis. History of epilepsy. Untreated depression. Uncontrolled diabetes (glucose <70 or >200 at screening). Use of interferon or ribavirin during study and for 1 month prior to screening. History of bipolar disorder, Alzheimer's dementia, ALS, Parkinson's disease or other medical dementias other than HIV-related. History of schizophrenia, mania or other serious mental illness. History of methylphenidate allergy. Other serious concurrent medical illness other than HIV. History of radiation therapy to the brain or brain injury. History of crystal methamphetamine, cocaine, LSD use or other recreational substance use other than marijuana within the 12 months prior to screening and for the duration of the study. Plan to use marijuana or marinol during the entire study duration and one month prior to screening visit. Plan to drink 7 or more alcoholic drinks per week during the 4 weeks prior to screen visit and for the duration of the study. History of alcohol dependence, alcohol abuse, cocaine addiction, crystal methamphetamine addiction or other recreational drug addiction or treatment for addiction or dependence within 5 years of screening visit. If subject is using prescription narcotics, should be on a stable dose for at least 1 month prior to screening and throughout the study. Previous use of Concerta™, Ritalin™, atomexitine or Adderall™ or other psychostimulants (e.g. modafinil, armodafinil) for 3 months prior to screening visit and for duration of the study. History of tic disorders in the past 3 months or any history of Tourette's syndrome. Greater than 10% below ideal body weight (IBW for men = 50 kg + 2.3 kg per inch over 5 feet of height, and IBW for women = 45.5 kg + 2.3 kg per inch over 5 feet of height) Uncontrolled migraine headaches. History of short gut syndrome, Meckel's diverticulum, or cystic fibrosis. Family history of sudden cardiac death in a young relative. History of fainting with exercise. History of attention deficit disorder will be excluded, defined as a score greater than 6 on the Childhood ADHD Symptoms Scale. - | 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): 18.0-80.0, Erectile Dysfunction Incomplete response to active treatment (not placebo) on first round but patient is still unsatisfied. 2. Recurring ED (had improved on first round of shock wave therapy but after a certain period of time became clinically worse again) after shock wave therapy. 3. A minimum of two sexual attempts per month. 4. An IIEF-ED domain score ≤ 25 post screening, with or without PDE5i intake according to assessment on final visit of Shockwave previous treatment. 5. A stable heterosexual relationship with the same partner for more than three months Subjects that did not respond at all to the first round as well as those that did not respond sufficiently. 2. Any pelvic surgery during the period after the first round. 3. Any unstable medical or psychiatric condition, spinal cord injury, or penile anatomical abnormalities arising during this period . 4. cardiovascular conditions that prevent sexual activity. 5. Recent Use of anti-androgens, or oral or injectable androgens 6. Recent hormonal, neurologic, or psychological pathology | 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, B-cell Chronic Lymphocytic Leukemia FOR BLAST (procurement) Patients with B-CLL (not in Richter's transformation) with measurable disease Procurement consent signed and faxed to Research Coordinator HIV negative (can be pending at this time) FOR AND (protocol entry) Manipulated B-CLL cells available (at least 6 injections) Patients with B-CLL (not in Richter's transformation) with measurable disease Patients must have a life expectancy of at least 10 weeks Patients must be less than 75 years old Patients must have ECOG performance status of 0-2 Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study FOR (protocol entry) Infected at time of protocol entry, or receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole) Pregnant or lactating Suffering from an autoimmune disease (including refractory immune thrombocytopenia-ITP or refractory autoimmune hemolytic anemia-AIHA) Receiving immunosuppressive drugs Received systemic steroids within 30 days of study enrollment Autologous hematopoietic stem cell transplant or fludarabine chemotherapy within 6 months of study enrollment History of allogeneic stem cell transplant Patients with congestive heart failure or significant arrhythmia Known hypersensitivity to thalidomide or lenalidomide | 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, Lymphoma Adult patients >18 years of age CD20+ low-grade (indolent) lymphoma of follicular and marginal zone type, small lymphocytic lymphoma without a B-CLL phenotype, or indolent lymphoma not otherwise specified Stage II (with bulky disease), III, or IV lymphoma No previous chemotherapy or a maximum of 6 months chlorambucil or cyclophosphamide Indication for treatment: symptomatic enlarged lymph nodes, spleen or other lymphoma manifestations, progression >6 months of lymphadenopathy or splenomegaly, anemia or thrombocytopenia or decreased hemoglobin or platelets due to lymphoma, general symptoms (weight loss, night sweats or fever) WHO performance status 0-2 Prior treatment with rituximab or an interferon B-CLL, mantle cell lymphoma, lymphoplasmacytic lymphoma (Waldenstroem's disease), or central nervous system lymphoma Indolent lymphoma transformed into aggressive lymphoma Indolent lymphoma with bulky tumor requiring urgent therapy Prior malignancies, except non-melanoma skin tumors, in situ cervical cancer, or curative surgery >5 years ago Positive for HIV infection Uncontrolled asthma or allergy requiring corticosteroids | 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 Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 for requiring treatment Measurable nodal disease by computed tomography Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen Eastern Cooperative Oncology Group Performance Status score of 0 or 1 Hematology and biochemical values within protocol-defined limits Agrees to protocol-defined use of effective contraception Women of childbearing potential must have negative blood or urine pregnancy test at screening Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy) Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib The presence of deletion of the short arm of chromosome 17 Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant Received a hematopoietic stem cell transplant Known central nervous system leukemia/lymphoma or Richter's transformation Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia Chronic use of corticosteroids History of prior malignancy, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease | 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): 20.0-74.0, Diabetes, Type 2 Patients who completed Study 262-09-001 (namely, patients who visited the hospital at visit Week 24） Patients who are capable of giving informed consent prior to participating in this clinical study Patients who are able to take contraceptive measures to avoid pregnancy of the patient or the patient's partner for the entire study period and for 4 weeks after the study (end of the post-observation period) Patients who withdrew from Study 262-09-001 Patients who experienced serious adverse events that the relationship with the study drug was not denied in Study 262-09-001 Patients who experienced serious adverse events that the relationship with the study drug are denied in Study 262-09-001 and whose symptoms are still emerged at the time of initiation of this study Patients who met the of Study 262-09-001 during the study period of Study 262-09-001 Female patients who wish to become pregnant during the study period of Study 262-09-002 or within 4 weeks after the study Patients otherwise judged by the investigator or subinvestigator to be inappropriate for in 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, Chronic Lymphocytic Leukemia Key Adults with previously treated recurrent CLL who have measurable lymphadenopathy Require therapy for CLL Have experienced CLL progression < 24 months since the completion of the last prior therapy Have disease that is not refractory to ofatumumab Note: Other protocol defined Inclusion/ | 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, Anemia Hematopoietic/Lymphoid Cancer Lymphopenia Neutropenia Thrombocytopenia No evidence of active disease as measured by staging studies pertinent to the particular diagnosis within 1 month of the CD 34+ boost 2. Full donor chimerism as manifested by a ≥ 90% donor peripheral blood total, MNC, and T cell chimerism result on the last two studies prior to the planned CD 34+ boost, with the second study performed within 1 month of the infusion. 3. HHV-6 and CMV negative by PCR for at least 1 month prior to the CD 34+ boost as measured by at least 2 assays within the month timeframe 4. ANC of < 1000 10^6/L or maintenance of an ANC ≥ 1000 10^6/L only with white cell growth factor support 5. Requirement for red cell transfusion to maintain a hemoglobin of ≥ 9.0 g/dL 6. Requirement for red cell transfusion to avoid symptomatic anemia in patients with hemoglobin values of ≤ 11.0 g/dL 7. Requirement for platelet transfusion to maintain a platelet count of ≥ 20 10^9/L 8. Requirement for platelet transfusion to avoid bleeding in patients with platelet counts ≤ 50 109/L 9. No signs of active acute GVHD (excluding stages I-II skin 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, Superficial Bladder Cancer Aged 18 years or older at the time of consent 2. Able to give informed consent 3. Subjects with high grade BCG-refractory or relapsed NMIBC including High grade non-invasive papillary carcinomas (Ta) and subjects with high grade tumors that invade sub-epithelial connective tissue (T1) or Carcinoma in situ (CIS) only or CIS and Ta or T1 tumors Refractory is defined as failure to achieve a disease-free state at six months after adequate induction of BCG therapy with either maintenance or re-induction at 3 months. Adequate induction is defined as a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a minimum of 2 out of 3 doses of treatment. Relapse is defined as recurrence within 1 year after a complete response to BCG treatment 4. Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment 5. Available for the whole duration of the study 6. Life expectancy >2 years, in the opinion of the investigator 7. ECOG status 2 or less 8. Absence of upper tract urothelial carcinoma 9. Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. 10. Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion. 11. Adequate laboratory values Hemoglobin ≥10 g/dL WBC ≥4000/μL ANC ≥2000/μL Platelet count ≥100,000/μL INR within institutional normal limits aPTT within institutional normal limits Current or previous evidence of muscle invasive or metastatic disease 2. Current systemic therapy for bladder cancer 3. Current or prior pelvic external beam radiotherapy 4. Prior treatment with adenovirus-based drugs 5. Suspected hypersensitivity to interferon alpha 6. Existing urinary tract infection or bacterial cystitis 7. Clinically significant and unexplained elevated liver or renal function tests 8. Women who are pregnant or lactating 9. Severe cardiovascular disease 10. History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin) 11. Subjects who cannot hold instillation for 1 hour 12. Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation 13. Intravesical therapy within 6 weeks of enrollment | 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): 19.0-60.0, Chronic Fatigue Syndrome Males and females 19-60 years old Hemoglobin concentration between 13 and 14 g/dL(men), 12 and 13 g/dL(women) Able to give informed consent Allergic or hypersensitive to any of the ingredients in the test products History of reaction to any of the test products or of gastrointestinal diseases such as Crohn's disease or gastrointestinal surgery Participation in any other clinical trials within past 2 months Laboratory test, medical or psychological conditions deemed by the investigators to interfere with successful participation in the study Pregnant or lactating women etc | 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, Lymphoid Malignancies Previously treated recurrent B-cell iNHL, DLBCL, MCL, HL or CLL Measurable lymphadenopathy Requires therapy Recent history of a major non-lymphoid malignancy Evidence of ongoing infection Concurrent participation in another therapeutic clinical trial | 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): 18.0-70.0, Cirrhosis of Liver Hepatic Encephalopathy Hepatic cirrhosis based on clinical, biochemical, radiological and/or histological data Patients with overt acute grade 2, 3 and 4 HE, according to the West Haven with or without precipitating factors Age of patient 18-70 years Patients who are terminally ill Acute on chronic liver failure Hepatocellular carcinoma Wilson's disease as the etiological factor of liver disease Advanced cardiac or pulmonary disease Presence of underlying chronic renal failure Neuro-degenerative disease or major psychiatric illness Patients on sedatives or antidepressants Pregnancy or breastfeeding | 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 (CLL) Patients must have diagnosis of CLL (as defined by the NCI below Patients must have peripheral blood absolute lymphocyte count of >5,000/mm3 obtained within 2 weeks prior to start of study The lymphocytosis must consist of small, mature lymphocytes, with ≤55% (not greater than 55%) prolymphocytes Patients must have phenotypically characterized CLL as defined as: 1. The predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.); 2. Surface immunoglobulin (slg) and CD20 with low-cell surface density expression. 3. If surface immunoglobulin can be demonstrated, the leukemic cells are restricted to expression of either kappa or lambda Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL Patients must require chemotherapy Patients must not have received prior treatment cytotoxic, immunotherapy or investigational therapy Patients must not have history of corticosteroid treatment for CLL, Autoimmune thrombocytopenia, or autoimmune hemolytic anemia Calculated creatinine clearance ≥30ml/min by Cockcroft-Gault formula Bilirubin must be ≤1.5mg/dl, unless secondary to tumor, obtained within 2 weeks prior to registration Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are not eligible No prior immunotherapy, investigational or cytotoxic chemotherapy Patients with a history of steroid treatment for CLL/SLL autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible Patients with active infections requiring oral or intravenous (IV) antibiotics until resolution of the infection and completion of therapeutic antibiotics Women of childbearing potential and sexually active males who both refuse to use an accepted and effective method of contraception or women who are breastfeeding Patients with a second malignancy other than basal cell carcinoma or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously History of known HIV History or presence CNS disease Evidence of laboratory TLS by Cairo-Bishop definition of Tumor Lysis Syndrome History of corticosteroid treatment for CLL, Autoimmune thrombocytopenia, or autoimmune hemolytic anemia | 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): 0.0-21.0, Diffuse Large B Cell Lymphoma Post Transplant Lymphoproliferative Disorder Primary Mediastinal (Thymic) Large B-cell Lymphoma Patient with newly diagnosed, histologically confirmed, Group B or C diffuse large B-cell lymphoma; or primary mediastinal B-cell lymphoma. Patients with Group B/C post transplant lymphoproliferative disorder are eligible for the study regardless of whether disease is newly diagnosed. (Murphy staging will be used for group classification.) Patient who has received previous chemotherapy or radiation therapy in the previous 3 months, except for empiric initial intrathecal administration at diagnosis. Rituximab or steroid administration is not an criterion Patient who has received any prior anthracyclines Patient with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction <28%) NOT due to mediastinal mass Patient with severe renal disease (i.e. creatinine greater than 3 times normal for age; creatinine clearance less than 50 ml/min/1.73m2) Patient with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST greater than 500 IU/L) Patient with a Karnofsky performance score <50% or Lansky score <50% HIV-positive patients will be excluded unless antiretroviral therapy can be safely withheld during chemotherapy administration, based on clinical determination of infectious disease team evaluation Female patient who is pregnant or breastfeeding Patient with reproductive potential not willing to use an acceptable method of birth control (i.e. hormonal contraception, intrauterine device, condom or diaphragm with spermicide, or abstinence) for the duration of the study and one year post completion of therapy Patient with primary central nervous system (CNS) lymphoma (lymphoma limited to the craniospinal axis without systemic involvement) | 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, Hepatocellular Cancer Histologically confirmed advanced HCC Barcelona Clinic Liver Cancer stage C or stage B if you cannot tolerate or failed TACE No cirrhosis or Child-Pugh A cirrhosis Measurable lesions All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 grade 1 or less Able to swallow and retain oral medication Prior systemic regimens for HCC Uncontrolled hypertension CLIP score > 3 ECOG PS > 1 Clinically apparent central nervous system metastases or carcinomatous meningitis Pregnant or breastfeeding Active or clinically significant cardiac disease Evidence or history of bleeding diathesis or coagulopathy Any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 4 weeks of enrollment Presence of a non-healing wound, non-healing ulcer, or bone fracture | 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, Waldenstrom Macroglobulinemia Histologically confirmed diagnosis of WM At least one prior systemic therapy Measurable disease, defined as quantifiable monoclonal IgM > 1000 mg/dL Active disease requiring therapy defined as at least one of the following five 1. Rising IgM 2. Hemoglobin < 20 g/dL 3. Platelet count < 100 x 109/L 4. Symptomatic or bulky lymphadenopathy or organomegaly 5. Systemic manifestations of WM, including hyperviscosity, neuropathy, amyloidosis, cryoglobulinemia, B symptoms note: subjects with symptomatic hyperviscosity or a serum viscosity of > 3.5 CP are eligible but should undergo plasmapheresis prior to initiation of treatment Understand and voluntarily sign an informed consent form Age >18 years at the time of signing the informed consent form Able to adhere to the study visit schedule and other protocol requirements ECOG performance status ≤ at study entry Laboratory test results within these ranges: 1. Absolute neutrophil count ≥ 1000/mm³ 2. Platelet count ≥ 50,000/mm³ 3. Creatinine clearance of ≥ 30 mL/min by Cockroft-Gault formula. 4. Total bilirubin ≤ 1.5 times the ULN, unless abnormality is the result of Gilbert's disease or the result of the WM 5. AST (SGOT) and ALT (SGPT) ≤ 3 x ULN Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study Concurrent use of other anti-cancer agents or treatments Prior treatment with thalidomide or lenalidomide Active serious infection not controlled with antibiotics Autoimmune hemolytic anemia or thrombocytopenia requiring treatment Known positive for HIV Active infection with hepatitis B, defined by being positive for HepBsAg or Hep B DNA by PCR, or hepatitis C Pre-existing peripheral neuropathy > grade 2 Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide and/or thalidomide) | 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): 16.0-65.0, Germ Cell Tumour Germ Cell Tumour (GCT) Relapsed or progression on or following platinum-based chemotherapy (rising tumour markers or progressive disease on PET CT Scan prior to entering study) Neutrophil count >1.0x109/l Platelets >70x109/l Haemoglobin >100g/l (may be transfused) Glomerular filtration rate >40ml/min (determined by EDTA clearance or calculated creatinine clearance using the Cockcroft Gault equation if unable to perform EDTA clearance) Males and females aged 16-65 years a) Male patients must have prognostic score, low to very high Patients must be sterile or agree to use adequate contraception during the period of therapy ECOG Performance status 0-3 Other malignancy except basal cell carcinoma Significant co-morbidity likely to make delivery of this treatment unsafe Currently enrolled in any other investigational drug study Previous chemotherapy with oxaliplatin, methotrexate or Actinomycin D Patients who have peripheral neuropathy with functional impairment | 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, Hyper-reactive Malarial Splenomegaly Malaria Anaemia Defining features of HMS including chronic massive splenomegaly (at least 10 cm below the costal margin); serum Immunoglobulin M elevated more than 3.1 g/L and high malarial antibody titres (above 640) Evidence of the polyclonal nature of the lymphocytes by serum immunoglobulin free light chains Aged at least 18 years Haemoglobin level of > 5 mg/d known allergy to chloroquine use of anti-malarial treatment within the preceding month suspected coexisting diseases in which glucocorticoids are contraindicated (e.g. diabetes mellitus, peptic ulcer disease or any acute infection as defined clinically), and splenomegaly secondary to known infectious or haematological causes | 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): 0.0-75.0, Non-Hodgkin Lymphoma Chronic Lymphocytic Leukemia Acute Lymphocytic Leukemia Referred patients (or respective donors) will initially be consented for procurement of blood for generation of the transduced ATL. at this stage Diagnosis of recurrent B-cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will high dose therapy and autologous stem cell transplantation CD19-positive tumor (result can be pending at this time) Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18 years) Hgb greater than or equal to 7.0 (can be a transfused value) If pheresis required to collect blood Creatinine < 1.5 x upper limit normal AST <1.5 × upper limit normal PT and APTT <1.5 × upper limit normal Informed consent explained to, understood by and signed by patient/guardian (and donor, where applicable). Patient/guardian given copy of informed consent Active infection requiring antibiotics No history of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry Currently receiving any investigational agents or received any tumor vaccines within the previous 6 weeks. (Note treatment with PD1/PDL1 inhibitors is allowed.) History of hypersensitivity reactions to murine protein-containing products Pregnant or lactating Tumor in a location where enlargement could cause airway obstruction Active infection with HIV or HTLV | 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-Hodgkin Lymphoma Participants with CD20-expressing B-cell NHL that is relapsed or refractory to standard therapy. Chronic lymphocytic leukemia/small lymphocytic lymphoma with peripheral blood leukemia/lymphoma cells and high-grade lymphomas are excluded. 2. Participants must have received prior rituximab-containing therapy. 3. Evaluable disease. In the absence of lymphadenopathy, splenomegaly with defects or measurable extra-medullary disease is acceptable. 4. Participants who have received a prior autologous stem cell transplant are eligible if the transplant occurred >6 months ago. 5. Participants who have received a prior allogeneic stem cell transplant are eligible if: 1. The transplant occurred >6 months ago 2. There is no evidence of active graft versus host disease 3. Systemic immunosuppressive agents (including corticosteroids) have not been received for at least 8 weeks 6. Karnofsky performance scale ≥70% 7. Life expectancy ≥12 weeks 8. Adequate baseline functions: 1. Serum creatinine ≤1.5 mg/deciliter (dL) 2. Total white blood cell (WBC) count ≥3000/microliter (µL) or absolute neutrophil count (ANC) ≥1000/µL 3. Absolute lymphocyte count ≥0.75 * 10^3/µL 4. Platelet count ≥75,000/µL 5. Hematocrit ≥25% or hemoglobin ≥9 grams/100 milliliters (mL) 6. Alanine aminotransferase (ALT) <2.5 * upper limit of normal (ULN) 7. Aspartate aminotransferase (AST) <2.5 * ULN 8. Total bilirubin (TBili) <1.5 * ULN 9. Sodium, potassium, and phosphorus levels no worse than grade 1 10. Chest x-ray (CXR) or computed tomography (CT) within 4 weeks prior to Day 1 with no evidence of pulmonary congestion, pleural effusions, pulmonary fibrosis, or significant emphysema. If results are questionable, participants should have additional lung function testing to clinically relevant restriction or obstruction. Participants must have a forced expiratory volume (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO) of at least 65% and 50% of expected, respectively. 11. Electrocardiogram (12-lead ECG) QTc ≤480 millisecond (ms) 12. Cardiac stress test (for example, stress thallium scan, stress echocardiography) with normal results if participant is suspected to have coronary artery disease. 9. Participants participating in the study are to use adequate birth control measures (abstinence, oral contraceptives, barrier method with spermicide or surgical sterilization) during the study. Females of childbearing potential must have a negative serum pregnancy test on the days of dosing. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (that is, has had menses at any time in the preceding 24 consecutive months). 10. Provide written informed consent prior to any screening procedures Evidence of central nervous system lymphoma or lymphomatous meningitis 2. Prior treatment with interleukin 2 (IL2) within the last 5 years 3. Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab 4. Pregnant or lactating female 5. An immediate need for palliative radiotherapy or systemic corticosteroid therapy 6. Known intercurrent infections (including hepatitis C virus and human immunodeficiency virus or other conditions), or clinical evidence of these conditions 7. Actively infected with or chronic carriers of hepatitis B virus as demonstrated by positive hepatitis B core antibody or hepatitis B surface antigen. Participants who are seropositive only, that is, surface antibody positive [HbsAb], are permitted. 8. Other significant active infection. 9. Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1 10. Uncontrolled hypertension (diastolic greater to or equal to 100 millimeters of mercury [mmHg]) or hypotension (systolic less than or equal to 90 mmHg) 11. History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias 12. History of medically significant ascites requiring repetitive paracentesis 13. Previous diagnosis of autoimmune disease (Exceptions: participants with autoimmune thyroiditis or vitiligo may be enrolled) 14. Organ transplant recipient 15. History of prior therapy or a serious, uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study 16. Known hypersensitivity to Tween-80 or human immunoglobulin 17. Legal incapacity or limited legal capacity 18. Participants with bulky lymph nodes (LNs) (≥10 centimeters [cm]) or marked splenomegaly (that is, extending into pelvis or crossing the midline). 19. Circulating levels of rituximab >75.0 micrograms (µg)/mL | 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, Cirrhosis Hepatic Encephalopathy Ambulatory patient with cirrhosis Able to provide informed consent History of alcohol abuse within six months Active gastrointestinal bleeding Unable to provide 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): 65.0-999.0, Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 that includes all of the following >= 5 x 10^9 B lymphocytes (5000/uL) in the peripheral blood On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of cluster of differentiation (CD)19 and CD20, as well as the T-cell antigen CD5; patients with bright surface immunoglobulin expression or lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by interphase cytogenetics Patients must be intermediate or high-risk Rai stage CLL Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia Patients must meet for treatment as defined by IWCLL 2008 guidelines which includes at least one of the following 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 | 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, Hypermetabolic Lymphadenopathy Mediastinum Lower, Posterior and Middle, Detected by PET-CT With 18F-FDG (PET) Any patients who have had PET showing one or more hypermetabolic lymphadenopathy in middle mediastinum and/or lower and/or posterior, and requiring diagnostic certainty for support. 2. PET scans performed in these particulars Pre-treatment assessment of thoracic or extra-thoracic malignancies (patients without a history of cancer) Evaluation of response to treatment referred to oncological Suspicion of relapse in patients with a personal history of thoracic or extra-thoracic malignancies. 3. PET, the result is positive For above-centimeter lymph node short axis: greater result than or equal to the background hepatic noise For sub-centimeter lymph node small axis : greater result than the background hepatic noise 4. Patient with indication of diagnostic procedure surgically (whether realized or not) 5. Lymph node(s) available(s) puncture by EUS esophageal, so for a technically feasible for esophageal puncture (without vascular recusants structures) 6. Age ≥ 18 years. 7. PET scan performed within 6 weeks before EUS 8. Platelets ≥ 70 000/mm3; TP ≥ 60%. 9. Patient of childbearing age with negative pregnancy test and / or a contraception. 10. Patient gave informed consent signed. 11. Patient affiliated to a social security scheme Contra-indication (s) Director (s) to achieve a EUS Balance adverse anesthetic (not allowing a general anesthetic) Esophageal stenosis Coagulation disorders Pregnant or lactating women Unable to undergo medical monitoring test for geographical, social or psychological reasons Private patient freedom and major subject of a measure of legal protection or unable to 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, Multiple Organ Failure Age ≥18 years Admitted to emergency department, Karlstad Central Hospital, Sweden Not in need of venous blood sample | 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, Non-Hodgkin Lymphoma Age ≥ 18 years. 2. Diagnosis of relapsed or refractory to previous therapy biopsy-proven Diffuse Large B cell non-Hodgkin's Lymphoma (there is no limit on the number of prior therapies. Subjects who have relapsed following an autologous stem cell transplant are eligible.) 3. Measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter. 4. ECOG (Eastern Cooperative Oncology Group) performance status score of 0, 1, or 2. 5. Life expectancy of >= 90 days (3 months). 6. Must be able to adhere to the study visit schedule and other protocol requirements. 7. Signed informed consent 8. Social security program affiliation 9. Females of childbearing potential (FCBP*) must have negative pregnancy test (sensitivity of at least 25 mIU/mL) prior to starting study drug in accordance with the Global Pregnancy Prevention Plan (PPP, annex 6) 10. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously** or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study drug; and 3) for at least 12 months after discontinuation from the study drug. Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy. Agree not to donate blood, semen or sperm while taking study drug and for 28 days after stopping study drug. Do not share drug with other person. Do not break, chew, or open study drug capsules. Return unused study drug capsules to the study doctor Any of the following laboratory abnormalities Absolute neutrophil count (ANC) < 1.5 x 109/L Platelet count < 60 x 109/L Calculated creatinine clearance (Cockcroft-Gault formula) of < 50mL/min Serum SGOT/AST or SGPT/ALT 5.0 x upper limit of normal (ULN) Serum total bilirubin > 2.0 mg/dL (34 μmol/L)/conjugated bilirubin >0.8mg/dL, except in case of hemolytic anemia. 2. Subjects who are candidates for and willing to undergo an autologous stem cell transplant. 3. Subjects who are post allogenic stem cell transplant. 4. All subjects with active central nervous system (CNS) lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible. (If required, lumbar puncture, CT or MRI should be performed during screening process.) Subjects should not be receiving corticosteroids. 5. Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for 5 years 6. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 7. Pregnant or lactating females. 8. Uncontrolled intercurrent illness including, but not limited to Ongoing, severe or active infection requiring antibiotics Uncontrolled diabetes mellitus as defined by the investigator Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease) Unstable angina pectoris, angioplasty, stenting, or myocardial infarctions within 168 days (6 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): 18.0-65.0, Rhinitis, Allergic, Perennial and Seasonal Diagnosis of Allergic Rhinitis (AR), as determined by the presence of seasonal or perennial rhinitis symptoms for several months per year, for more than 1 year and are not attributed to infections or nasal abnormalities Subjects have a TNSS score of >=6 at the baseline screening allergen challenge. Total nasal symptom score is the sum of nasal congestion, rhinorrhoea, nasal itch and sneeze, each of which are scored on a scale from 0 to 3 Subjects have a positive skin prick test (wheal >=4 millimeter [mm]) for seasonal pollen at or within the 12 months preceding the screening visit Subjects have a positive radioallergosorbent test (RAST) (>=class 2) for seasonal pollen at or within the 12 months preceding the screening visit There are no conditions or factors that would make the subject unlikely to be able to stay in the chamber for 4 hours Male/females between 18 and 65 years of age inclusive, at the time of signing the informed consent Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the or outside the reference range for the population being studied may be included only if the Investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19 kg per meter square (m^2) (inclusive) A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy (for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study as obtained via a verbal interview with the subject or from the subject's medical records); or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international unit per milliliter (MlU/mL) and estradiol <40 picogram (pg)/mL (<147 picomol per liter [pmol/L]) is confirmatory); child-bearing potential with negative pregnancy test as determined by urine human chorionic gonadotropin (hCG) test at screening or prior to dosing and agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 1 week post-last dose Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Subjects should be non-smokers, which for this study is defined as having smoked <10 packs per year in their lifetime, and have not smoked in the 6 months prior to the screening visit Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin <=1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) Based on single or averaged corrected QT interval (QTc) values of triplicate electrocardiogram (ECGs) obtained over a brief recording period: Fridericia QTc (QTcF) <450 milliseconds (msec) Nasal abnormalities likely to affect the outcome of the study, i.e. nasal septal perforation, nasal polyps, sinusitis and other nasal malformations History of frequent nosebleeds | 0 |
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