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The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Atrial Fibrillation ≥ 18 years of age Patients of African, European, and Hispanic descent History of typical or early-onset symptomatic (≥2 episodes/month) paroxysmal/persistent AF ECG that was recorded within 1 month of randomization showing AF Eligible for both Flecainide(Class I) and Sotalol (Class III) AAD Able to give informed consent Permanent AF or isolated atrial flutter Cardiac or thoracic surgery within the previous 6 months Previous use of amiodarone other than short-term use (e.g. for an acute arrhythmia in hospital) Medical condition that is likely to be fatal in less than one year A history of prior AF ablation Have already been tried on 2 or more AADs in the past for AF Creatinine clearance <40 ml/min Left ventricular ejection fraction < 50% Contra-indication to a Class I AAD e.g., structural heart disease, or history of MI Contra-indication to a Class III AAD, e.g., congenital or acquired long QT syndrome with QTc>480 ms in females and >460 ms in males at baseline | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 8.0-60.0, Pompe Disease Males or females between 8 and 60 years of age; 2. Diagnosis of Pompe disease (protein assay, genotyping, and positive clinical signs) 3. No contraindication to pyridostigmine Already receive pyridostigmine as part of their normal clinical care at screening 2. Are pregnant participants will receive a urine pregnancy test at screening 3. Have received acute administration of antibiotic, corticosteroid, or neuromuscular blockade medications within 30 days prior to screening 4. Any other concurrent medical condition which, in the opinion of the study team, would make the subject inappropriate to participate in the assessments | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 15.0-55.0, Pompe Disease Glycogen Storage Disease Type II Lysosomal Storage Diseases Male or female subjects 15-55 years of age Have a diagnosis of Pompe disease, as defined by protein assay and/or DNA sequence of the acid alpha-glucosidase gene, with present clinical symptoms of the disease Be naïve to ERT or receiving ERT for at least eighteen months prior to beginning study Be able to walk at least 40m in the 6 minute walk test Willing to comply with study requirements Be pregnant Be in the lower limit for pulmonary function; FVC < 30% predicted Be dependent on assisted ventilation Be dependent on wheelchair Have evidence of clinical heart failure Have any contraindication to exercise | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 12.0-90.0, Muscle Weakness Subjects who have been taking pyridostigmine for the treatment of any condition other than myasthenia gravis Subjects taking pyridostigmine for the treatment of myasthenia gravis will be excluded | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 1.0-20.0, Advanced Malignant Solid Neoplasm Recurrent Brain Neoplasm Recurrent Malignant Solid Neoplasm Refractory Brain Neoplasm Patients must be >/= 12 months and < 21 years of age at the time of study enrollment Patients must have had a previous histological verification of a solid tumor at the original diagnosis and/or recurrence including brain tumors; for patients with brain stem gliomas and optic pathway tumors, the requirement for histological evaluation may be waived; the patient's disease must be considered refractory to conventional/standard therapy, or a disease for which no conventional therapy exists and is progressive The patient must have a stable clinical (neurologic in case of brain tumors) exam and be on a stable dose of steroids for at least 1 week prior to study entry; the patient should have a measurable and/or evaluable disease; measurable disease which is defined as the presence of at least one lesion that can be accurately measured in two dimensions (each measures at least 10 mm) or evaluable disease which is defined as at least one lesion that can be accurately measured in at least one dimension (measure at least 10 mm) Karnofsky performance status >= 50 for patients >= 16 years of age and a Lansky performance status >= 50 for patients aged < 16 years Life expectancy: must be >= 12 weeks Chemotherapy Must not have received myelosuppressive chemotherapy within 3 weeks of the study entry (6 weeks if prior nitrosourea); prior treatment with either dasatinib or temsirolimus but not both is allowed; at least 3 weeks must have elapsed from the last dose Biologic therapy (anti-neoplastic) Must not have received oral tyrosine kinase inhibitors (other than dasatinib) or other similar agents within 3 weeks of the study entry and all toxicities must have resolved to < grade 2 prior to enrollment Must not have received bevacizumab or other monoclonal antibody therapy within 4 weeks of study the entry Patients with evidence of recent intratumoral hemorrhage (within 3 months of study enrollment), gastrointestinal bleeding, history of coronary artery disease or on anticoagulation therapy Pregnant or breast-feeding women will not be entered on this study Uncontrolled current illness including, but not limited to, uncontrolled infection, need for hemodialysis, need for ventilatory support, psychiatric illness/social situations that would limit compliance with study requirements History of hypersensitivity to any component of the formulation Patients with known human immunodeficiency virus (HIV) are ineligible for this study Patients must not have received prior therapy with dasatinib and temsirolimus for any indication Patients with clinically significant cardiovascular disease: history of ischemic or hemorrhagic stroke within past 6 months; uncontrolled hypertension, on at least 2 repeated determinations on separate days within past 3 months; myocardial infarction or unstable angina within past 6 months; New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months; clinically significant peripheral vascular disease within past 6 months; pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past 6 months; diagnosed congenital long QT syndrome; any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); prolonged QTc interval on pre-entry electrocardiogram (> 450 msec); subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration Anticonvulsants: patients on enzyme inducing anticonvulsants (EIAED) will be excluded; if patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for >= 2 weeks prior to initiation of dasatinib Anticoagulants/anti-platelets: patients on therapeutic (treatment) dose of anticoagulants (e.g. warfarin, low molecular-weight heparin) are not eligible; patients are not allowed to take aspirin, clopidogrel, ticlopidine, Aggrenox; patients on prophylactic anticoagulation may be enrolled and treated on study as long as their platelet count is monitored closely and maintained at > 75,000 while they are receiving dasatinib Inducers and Inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4): patients required to be on any CYP3A4/5 inhibitors or inducers will be excluded (with the exception of dexamethasone, but all efforts should be made to reduce the dose of dexamethasone); patients must discontinue drug at least 7 days prior to starting dasatinib | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-70.0, Metastatic Thyroid Cancer Unresectable thyroid cancer expressing TG as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue. 2. Recurrent/metastatic radioiodine refractory disease that has progressed within the past 6 months with at least 1 lesion increasing by 0.5cm in diameter or with increasing bone metastases. 3. Confirmation of diagnosis of thyroid cancer by the Laboratory of Pathology of the NCI. 4. PET avid disease with SUV >5. 5. Patients must have previously received standard systemic therapy for advanced thyroid cancer (to radioactive iodine for iodine-avid tumors and surgery (if indicated)) and have been either non-responders (progressive disease) or have recurred. 6. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. 7. Greater than or equal to 18 years of age and less than or equal to 70 years of age. 8. Willing to sign a durable power of attorney 9. Able to understand and sign the Informed Consent Document 10. Clinical performance status of ECOG 0 or 1 11. Life expectancy of greater than three months 12. Patients must be HLA-A*0201 positive 13. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment. 14. Serology Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. o. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. p. Hematology Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim WBC less than or equal to 3000/mm3 Platelet count greater than or equal to 100,000/mm3 Hemoglobin greater than 8.0 g/dl q. Chemistry Serum ALT/AST less than or equal to to 2.5 times the upper limit of normal Serum creatinine less than or equal to to 1.6 mg/dl Total bilirubin less than or equal to to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl. r. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 3. Active systemic infections (e.g. : requiring anti-infective treatment), coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease. 4. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities). 5. Concurrent systemic steroid therapy. 6. History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine. 7. History of coronary revascularization or ischemic symptoms 8. Documented LVEF of less than or equal to 45%. Testing is required in patients with Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block Age greater than or equal to 60 years old | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 13.0-44.0, Pregnancy Smoking Cessation pregnant, 2. smoke or quit in the past 2 weeks, 3. has a data plan or an unlimited text messaging plan on her cell in order to avoid charges for texts, 4. an English speaker not pregnant 2. not currently smoking (or within past 2 weeks) 3. not able to receive text messages 4. not an English speaker | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-85.0, Inherited Cardiac Arrythmias Long QT Syndrome (LQTS) Brugada Syndrome (BrS) Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Early Repolarization Syndrome (ERS) Arrhythmogenic Cardiomyopathy (AC, ARVD/C) Hypertrophic Cardiomyopathy (HCM) Dilated Cardiomyopathy (DCM) Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy) Normal Control Subjects All patients and family members 18 years of age or older with inherited cardiac arrhythmias including LQTS, Brugada Syndrome (BrS), cathecholaminergic polymorphic ventricular tachycardia (CPVT) or early repolarization syndrome (ERS) are eligible for enrollment All enrolled patients will have undergone clinically indicated genetic testing Age <18 years >85 years pregnant women life-limiting co-morbidities immunocompromise | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis Exacerbations Was male or female aged ≥18 years Subjects must be willing and able to provide written informed consent (if applicable, a legally authorized representative may provide informed consent on behalf of the subject) Subjects who met the clinical for diagnosis of MG with an exacerbation defined as worsening of MG symptoms as defined by an Myasthenia Gravis Foundation of America (MGFA) classification IVb or V Subjects on long-term (8 weeks) corticosteroid treatment for MG Female subjects of child-bearing potential must have a negative test for pregnancy (human chorionic gonadotropin [HCG]-based assay) Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and long-term storage of extra samples, for the entire duration of the study Subjects who had received immune globulin treatment given by IV, subcutaneous or intramuscular route within the last 30 days Subjects with documentation of a lack of clinical response to intravenous immunoglobulin (IVIg) therapy for MG Subjects documented positive for antibodies directed against Muscle specific kinase (MuSK) Subjects with corticosteroid (CS) treatment initiated within the last 8 weeks or modified within the last 2 weeks Subjects with plasma exchange (PLEX) within the last 30 days Subjects with MG exacerbation attributable to change in medication or infection or evident infection as defined by, but not limited to, the presence of at least one of the following diagnostic features: 1) axillary temperature ≥38°C, 2) positive blood culture of infective microorganism, 3) white blood cell count >12×10^9/L and differential white blood cell count of >10% band neutrophils (>1.2×10^9/L), and 4) pulmonary infiltrate with consolidation on chest X-ray. Alternatively, other signs and symptoms may be considered for the diagnosis of evident infection according to the Investigator's judgement Subjects with inadequate venous access Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived product Subjects with a history of intolerance to any component of the investigational products Subjects with a documented diagnosis of thrombotic complications to polyclonal IVIG therapy in the past | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Cord Blood Collection Cesarean Elective cesarean deliveries Women with a blood count results maximum 30 days prior to delivery Emergent cesarean deliveries Cesarean deliveries due to placental adhesion abnormalities or placenta previa Patients on anticoagulation regimens Postpartum bleeding due to uterine atony, retained placenta Patients with a history of bleeding 30 days prior to delivery | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-65.0, Multiple Sclerosis for MS Group (20 women) 1. Patients with relapsing remitting multiple sclerosis. 2. Age 18 to 65 years 3. Diagnosed with motor fatigue in multiple sclerosis > 6 weeks. Motor fatigue equates to muscle fatigue due to physical exertion and is alleviated with rest and associated with fatigability. 4. Has a fatigue severity scale score (FSS) of ≥5. 5. Ambulatory with Expanded Disability Status Scale score (EDSS) 1.5 -6.5. for Control Group (10 women) 1. Female with no history of multiple sclerosis and no complaint of fatigue 2. Age 18 to 65 years Patients with MS exacerbation or corticosteroid treatment within one month before the study. 2. Patients with history or current diagnosis of Untreated thyroid disease Untreated vitamin D deficiency pregnancy taking over the counter energy booster in the last 1 week taking medication that will improve the function of the neuromuscular junction (i.e. pyridostigmine, steroid, rituximab, mycophenolate mofetil, azathioprine) myasthenia gravis symptoms or history of polyneuropathy involving the upper extremities myopathy symptoms or history suggestive of C7, C 8 radiculopathy | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Advanced Digestive System Neuroendocrine Neoplasm Duodenal Neuroendocrine Tumor G1 Functional Pancreatic Neuroendocrine Tumor Gastric Neuroendocrine Tumor Intermediate Grade Lung Neuroendocrine Neoplasm Low Grade Lung Neuroendocrine Neoplasm Nonfunctional Pancreatic Neuroendocrine Tumor Thymus Neoplasm Histologically or cytologically confirmed low or intermediate grade, unresectable well differentiated foregut neuroendocrine tumors (thymic, bronchopulmonary, gastric, duodenal and pancreatic); patients with multiple neuroendocrine tumors associated with MEN1 syndrome will be eligible Patients must have radiographically measurable disease Pancreatic neuroendocrine patients must have had progression after prior therapy; patients with other foregut neuroendocrine tumors must have had progressive disease over the last 12 months, irrespective of prior therapy; patients with both functional (who may continue somatostatin analogues as required for control of related symptoms) and non-functional tumors are eligible; in patients who have previously received therapy, the number of prior lines of therapy should not be more than 2 lines of systemic therapy not including somatostatin analogues Written informed consent must be obtained prior to any screening procedures Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment, to allow the effects of prior therapy to have abated: a) cytotoxic or targeted chemotherapy: greater than or equal to the duration of the cycle of the most recent treatment regimen (a minimum of 3 weeks for all regimens, except 6 weeks for nitrosoureas and mitomycin-C); b) biologic therapy (e.g., antibodies): greater than or equal to 4 weeks Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L Hemoglobin (Hgb) greater than or equal to 9 g/dL Platelets greater than or equal to 100 x 10^9/L Serum total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) Patient has a known hypersensitivity to LEE011 or any of its excipients Patients with known or suspected brain metastases; however, if radiation therapy and/or surgery has been completed and serial evaluation by computed tomography (CT) (with contrast enhancement) or magnetic resonance imaging (MRI) over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled; such patients must have no need for treatment with steroids or anti-epileptic medications Patients with concurrent malignancies or malignancies within 3 years prior to starting study drug (with the exception of tumors common to a single genetic cancer syndrome, i.e. MEN1, MEN2, von Hippel-Lindau [vHL], tuberous sclerosis complex [TSC] etc., or adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer) Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C (testing is not mandatory) Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (e.g. chronic pancreatitis, chronic active hepatitis, etc.) Patient who has received radiotherapy within less than or equal to 4 weeks or limited field radiation for palliation within less than or equal to 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions alopecia) and/or in whom greater than or equal to 30% of the bone marrow was irradiated Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery) Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis less than 12 months prior to screening b) history of documented congestive heart failure (New York Heart Association functional classification III-IV) c) documented cardiomyopathy d) patient has a left ventricular ejection fraction (LVEF) less than 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening e) history of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT syndrome or conduction abnormality within 12 months prior to starting study drug f) congenital long QT syndrome or a family history of corrected QT interval (QTc) prolongation g) on screening, inability to determine the corrected QT for Fridericia (QTcF) interval on the electrocardiogram (ECG) (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia's correction); all as determined by screening ECG (mean of triplicate ECGs) Systolic blood pressure greater than 160 mmHg or less than 90 mmHg at screening | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Hepatomegaly Myelofibrosis Transformation in Essential Thrombocythemia Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase Primary Myelofibrosis Splenomegaly Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS) Previously treated with ruxolitinib (unless not a good candidate for ruxolitinib therapy in the judgment of treating physician) Palpable splenomegaly or hepatomegaly of more than or equal to 5 cm below left or right, respectively, costal margin on physical exam Understanding and voluntary signing an institutional review board (IRB)-approved informed consent form No prior history of immune checkpoint modulator therapy Disease-free of other malignancies Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Negative pregnancy test in females of childbearing potential (FCBP); male patients with female partners of child-bearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 23 weeks (for females) or 31 weeks (for males) following the last dose of study medication; acceptable forms of contraception 1 highly effective method such as an intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, or partner's vasectomy and at least 1 additional approved barrier method such as a latex condom, diaphragm, or cervical cap plus spermicide; female patients of childbearing potential must not be breast-feeding or planning to breast feed and must have a negative pregnancy test within 24 hours of the first study treatment Direct bilirubin equal to or less than 1.5 x upper limit of normal (ULN) Serum creatinine equal to or less than 1.5 x ULN Use of any other standard or experimental therapy within 14 days of starting study therapy Lack of recovery from all toxicity from previous therapy to grade 1 or baseline Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease and study treatment-related toxicities Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to their first dose of the study drugs Patients who are currently receiving chronic (> 14 days) treatment with corticosteroids at a dose equal to or more than 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug Patients with autoimmune diseases are excluded: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis) Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-human chorionic gonadotropin (HCG) laboratory test Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C The use of dietary supplements or herbal medications within 7 days of starting study therapy | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 9.0-17.0, Narrative Exposure Therapy Treatment as Usual 17 years old has spent some part of her/his life living in a country where organized violence was taking place, or at a refugee camp suffers from significant stress symptoms thought be trauma-related acute psychosis intellectual disability | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Extremities Neoplasms Extremities Neoplasms diagnosed by positive biopsy or non-invasive Not suitable for surgical resection Eastern Cooperative Oncology Group (ECOG) score of 0-1 A prothrombin time ratio > 50% Platelet count > 80x10^9/L Ability of patient to stop anticoagulant and anti-platelet therapy for seven days prior to and seven days post NanoKnife procedure Able to comprehend and willing to sign the written informed consent form (ICF) Have a life expectancy of at least 3 months Cardiac insufficiency, ongoing coronary artery disease or arrhythmia Any active implanted device (eg Pacemaker) Women who are pregnant or women of child-bearing potential who are not using an acceptable method of contraception Have received treatment with an investigational agent/ procedure within 30 days prior to treatment with the NanoKnife™ LEDC System Are in the opinion of the Investigator unable to comply with the visit schedule and protocol evaluations | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 15.0-45.0, HIV HIV Infections Pregnancy Infant, Newborn, Diseases HIV positive Pregnant Attended an antenatal care visit at one of three participating clinics Not HIV positive Not pregnant Not registered for antenatal care at a participating clinic | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-80.0, Chronic Inflammatory Demyelinating Polyneuropathy To qualify, a patient must have CIDP and persistence of significant symptoms (having 2 or more of the following) Weakness in any limb Motor fatigue significant to interfere with ADL or work Paresthesia of sufficient severity to require a medication Sensory impairment Walking impairment, AND requires IVIG to control symptoms Thrombocytopenia or other bleeding disorders, 2. Anticoagulation therapy, 3. Severe or anaphylactoid reactions to IVIG, 4. Cancer, 5. Pregnancy, 6. Breast-feeding, 7. Renal insufficiency or failure, 8. Congestive heart failure, 9. Psychiatric illness | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 11.0-18.0, Tobacco Use Cessation Tobacco Prevention Ages 11 through 18 (11 and 18 included) 2. High school and Middle School students are both eligible 3. All 150 are nonsmokers. Nonsmokers are defined as individuals who have not smoked, not even part of a cigarette in the past year. 4. All will score above the median on smoking susceptibility 5. 10 will be White/Caucasian participants, 5 will be African American participants, 10 will be Hispanic participants, and 5 will be Asian participants. 6. English speaking None | 2 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis Auto-immune myasthenia gravis Age ≥ 18 years old Clinical Classification (MGFA) I-IV French speaking cognitive or visual impairment which would limit the capacity to fill out the MGQOL-15-F | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-85.0, Myasthenia Gravis, Generalized Anti-acetylcholine receptor (AChR) antibody positive Confirmed diagnosis of generalized myasthenia gravis (MG) Myasthenia Gravis Foundation of America (MGFA) classification of Class II, III, or IVa inclusive at Screening QMG >= 10 at Screening. Note: Subjects who only have a history of ocular MG may not enroll Receiving standard of care MG treatment at a stable dose consisting of any one of the following for the time intervals delineated below (time intervals apply to medications and maintenance of stable dose level): 1. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening and no immunosuppressants 2. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening AND/OR only one of the following: 1. Prednisone (up to 60 mg/day or equivalent) for at least 2 months prior to Screening, OR 2. Azathioprine for at least 6 months prior to Screening, OR 3. Mycophenolate mofetil for at least 6 months prior to Screening, OR 4. Methotrexate for at least 6 months prior to Screening, OR 5. Cyclosporine or tacrolimus for at least 3 months prior to Screening 3. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening AND/OR prednisone (up to 60 mg/day or equivalent) for at least one month prior to Screening and only one of the following: 1. Azathioprine for at least 6 months prior to Screening, OR 2. Mycophenolate mofetil for at least 6 months prior to Screening, OR 3. Methotrexate for at least 6 months prior to Screening, OR 4. Cyclosporine or tacrolimus for at least 3 months prior to Screening Have received cyclophosphamide or any other immunosuppressive agent apart from the ones allowed per within the past 6 months Any change in MG treatment regimen between Screening (Week -3, Visit 0) and Baseline (Week 0, Visit 1) Greater than two point change in QMG score, increased or decreased, between Screening (Week -3, Visit 0) and Baseline (Week 0, Visit 1) Any episode of myasthenic crisis in the one month prior to Screening Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during the course of the trial (intent to perform thymectomy) Thymectomy within the preceding 6 months Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months Have received immune globulin (Ig) treatment given by intravenous (IV), subcutaneous, or intramuscular route within the last 3 months Current known hyperviscosity or hypercoagulable state Currently receiving anti-coagulation therapy (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [e.g., dabigatran etexilate, rivaroxaban, edoxaban, and apixaban], parenteral anticoagulants [e.g., fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlodipine) | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Abdominal Aortic Aneurysms Diagnosed abdominal aortic aneurysm with indication for endovascular repair. 2. Intention to electively implant the Aorfix™ Stent Graft System Does not comply with the indications for Aorfix™ in the Instructions for Use (IFU). 2. Unwillingness or inability to comply with the recommended follow-up assessments according to the standards of care at the investigative site. 3. Unwillingness or inability to provide informed consent to both the Registry and the EVAR procedure. 4. Patients in whom Aorfix™ is being placed as a secondary procedure to a previous surgical or endovascular treatment of an AAA other than with another Aorfix™ graft | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 9.0-999.0, Acne Vulgaris Male or female at least 9 years of age and older Written and verbal informed consent must be obtained Subject must have a score of moderate or severe on the Evaluator's Global Severity assessment at the screening and baseline visit Pre-menses females and women of childbearing potential must have a negative urine pregnancy test at the screening and baseline visits Subjects must be willing to comply with study instructions and return to the clinic for required visits Any dermatological conditions on the face that could interfere with clinical evaluations Any underlying disease(s) or some other dermatological condition of the face that requires the use of interfering topical or systemic therapy or makes evaluations and lesion count inconclusive Subjects with a facial beard or mustache that could interfere with the study assessments Concomitant use of potentially irritating over-the-counter products | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 11.0-56.0, Abortion Pregnancy Tests She has been determined by the site investigator or designee to be fully eligible for medical abortion with mifepristone followed by misoprostol according to the site's standard criteria She is willing to use the semiquantitative pregnancy test at home She is wiling and able to comply with the study procedures She speaks and reads English She has signed the study informed consent form | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 20.0-999.0, Helicobacter Pylori Infection Consecutive H pylori-infected outpatients, at least 20 years of age, with endoscopically proven peptic ulcer diseases or gastritis previous H pylori-eradication therapy ingestion of antibiotics or bismuth within the prior 4 weeks patients with allergic history to the medications used patients with previous gastric surgery the coexistence of serious concomitant illness (for example, decompensated liver cirrhosis, uremia) pregnant women | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 16.0-999.0, Human Cancers Histologically or cytologically-proven advanced, unresectable solid tumour of a type known to express FRα in a percentage of cases 2. Archival tumour tissue expressing FRα (1+, 2+ or 3+ membrane staining on at least 5% of tumour cells by immunohistochemistry using the BN3.2 antibody, based on the technique described by Lawson & Scorer, 2010). 3. Advanced disease for which no alternative therapy is felt to be appropriate. 4. Measurable disease or disease evaluable by tumour marker. Measurable disease is preferred for patients entering higher cohorts to facilitate efficacy assessments. 5. World Health Organisation (WHO) performance status of 0 or 1 and a life expectancy of at least 12 weeks. 6. Haematological and biochemical indices within the ranges shown below. These measurements should be performed within 7 days before the first dose of MOv18 IgE (Day -7 to Pre-dose on Day 1). Measurements performed before Day -7 may be accepted by the CDD to demonstrate if repeat testing is logistically difficult for the patient and is not considered necessary medically in the opinion of the Investigator or CDD. Laboratory Test Value required Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN unless raised due to liver metastases in which case up to 5 x ULN is permissible Serum creatinine ≤ 1.5 x ULN 7. Aged 16 years or over at the time consent is given. 8. Written (signed and dated) informed consent and capable of co-operating with treatment and follow-up Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas and mitomycin-C) and investigational medicinal products during the previous 4 weeks, or 5 product half-lives before treatment. 2. Patients on beta-blockers and unable to interrupt beta-blockade (which may counteract the therapeutic effects of adrenaline), or tricyclic anti-depressants/MAOIs (which can dangerously augment the effects of adrenaline). These agents should be discontinued at least 4 half-lives before administration of the first dose of MOv18 IgE and for the duration of MOv18 IgE therapy. 3. Patients on bisphosphonates or treated with bisphosphonates in the last 18 months. 4. Ongoing toxic manifestations of previous treatments that have not resolved to Grade 1 or lower (other than alopecia of any grade or Grade 2 peripheral neuropathy). 5. Known brain metastases that have not been previously treated and been stable for at least 2 months. 6. Female patients who are able to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom; have an intra-uterine device and condom; diaphragm with spermicidal gel and condom) effective at the first administration of IMP, throughout the study and for six months afterwards are considered eligible. 7. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception at the first administration if IMP, throughout the study and for six months afterwards) or agree to sexual abstinence*. Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate. * Abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 8. Major thoracic or abdominal surgery from which the patient has not yet recovered. 9. At high risk from the effects of anaphylaxis because of non-malignant systemic disease including active uncontrolled infection, cardiac failure, peripheral vascular disease, previous cerebrovascular accident (CVA), dyspnoea due to heart failure, extensive lung metastases, significant pleural effusions or other conditions. 10. History of laryngeal oedema, uncontrolled or high risk asthma (according to Global Initiative for Asthma (GINA) guidelines), or anaphylaxis. Patients with a history of hypersensitivity to carboplatin, taxanes, or contrast media may enter the study at the investigator's discretion. 11. Patients with any congenital or acquired immunodeficiency syndrome or receiving immunosuppressive therapy (including any dose of systemic corticosteroids), or who are immunosuppressed post organ transplant. However, patients receiving inhaled corticosteroids and patients with a history of allergy (other than anaphylaxis) are eligible, as are patients with a history of auto-immune disease. 12. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 13. Patients with baseline elevation in serum tryptase (indicating possible mastocytosis) or a positive baseline basophil activation test (indicating a hypothetical potential for anaphylaxis with MOv18 IgE). 14. Participating or planning to participate in another interventional clinical trial, whilst taking part in this study. Participation in an observational study or in the follow-up phase of a previous interventional trial is acceptable. 15. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study. 16. Patients unwilling or unable to interrupt antihistamines (which may interfere with skin prick testing). Antihistamines should be discontinued at least 4 half-lives before the first skin prick test | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-18.0, Soft Tissue Neoplasms Bone Neoplasms Patients whose age less than 19 years Patients diagnosed with bone & soft tissue neoplasms involving the extremities Patients whose age more than 19 years Patients diagnosed with bone & soft tissue neoplasms not involving the extremities | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-85.0, Myasthenia Gravis, Generalized Diagnosis of MG class IIa to IVa inclusive (Myasthenia Gravis Foundation of America Clinical Classification). 2. Quantitative Myasthenia Gravis (QMG) score of 10 or greater. If the QMG score is < 15 no more than 4 points may be derived from items 1 or 2 (ocular motility disturbance and ptosis). 3. Documented history of acetylcholine receptor (AChR) or Muscle Specific Kinase (MuSK) antibody positive. 4. Only one immunosuppressant or immunomodulatory drug at a stable dose is allowed during the study (i) azathioprine and mycophenolate mofetil must be stable for at least 4 months prior to randomization (ii) cyclosporine must be stable for at least 3 months prior to randomization. 5. If the patient is on oral corticosteroids, methotrexate or tacrolimus at screening, the dose must be stable for at least 1 month prior to randomization. 6. If the patient is on cholinesterase inhibitors at screening, the dose must be stable for at least 2 weeks prior to randomization. 7. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, may be included in the study if they are using highly effective methods of contraception during the study and for 12 weeks after study treatment MGFA grade I, IVb, or V disease. 2. Documented presence of unresected thymoma. 3. Patients having undergone thymectomy or thymo thymectomy (resection of thymoma) within 6 months of screening. 4. Patients having received any of the following treatments prior to randomization: 1. IVIg or plasma exchange within 8 weeks; 2. oral or IV cyclosphosphamide treatment within 3 months; 3. IV corticosteroid bolus (dose higher than 1 mg/kg) within 3 months; 4. belimumab within 6 months. For patients who received belimumab earlier, B cell count should be within normal range; 5. rituximab within 12 months. For patients who received rituximab earlier, B cell count should be within normal range; 6. any other biologic or an investigational drug within 1 month or five times thehalf-life, whichever is longer. 7. Live vaccines within 4 weeks of study drug infusion. 5. Patients who are at significant risk for TE as judged by the investigator or have any one of the following: 1. History of either thrombosis or 3 or more spontaneous abortions with or without the presence of anti-cardiolipin autoantibodies; 2. Presence of prolonged partial thromboplastin time (PTT) | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 13.0-45.0, Von Willebrand Diseases Adult females 13-45 years of age. 2. Mild or moderate von Willebrand disease (VWF:RCo <0.50 IU/ml, normal multimers, past bleeding) 3. Menorrhagia defined as PBAC >100 in at least one of the last two menstrual cycles. 4. Regular menses, at least every 21-35 days. 5. Willingness to have blood drawn 6. No prior history of an allergic reaction or anaphylaxis to rVWF or TA. 7. Willingness to avoid aspirin (ASA) and nonsteroidal anti-inflammatory agents (NSAIDS) during the study. 8. Willingness to comply with randomization to rVWF or TA study arms. 9. Willingness to keep a personal diary of menorrhagia bleeding frequency duration and severity by pictorial blood assessment chart, and any drugs or hemostatic agents taken. 10. Willingness to make 4 visits and undergo blood sampling for coagulation studies, and accept randomization of two therapies for each of four consecutive menstrual cycles, including an end-of-study visit. 11. Willingness to use "double-barrier" method of contraception during the study Any bleeding disorder other than von Willebrand disease; or past thrombotic disease 2. Pregnant or lactating, or use of hormones (other than progesterone-only), or combined oral contraceptives, and contraceptive implants in past 3 months. 3. Platelet count < 100,000/ul. 4. Use of immunomodulatory or experimental drugs. 5. Surgery within the past 8 weeks. 6. Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs. 7. Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing VWF within 5 days of study. 8. Inability to comply with study requirements. 9. Hypothyroidism as defined by elevated TSH. 10. Iron deficiency as defined by low serum ferritin, unless iron replacement has been initiated. 11. History of renal disease | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-64.0, Myasthenia Gravis Male and female subjects, with ocular and generalised myasthenia gravis (grade 1-2-3) Between the ages of 18 and 64 years, inclusive, at the time of the first injection A Body Mass Index (BMI) between 18 and 35 kg/m2, inclusive Patient with positive antibodies to AChR based on radioimmunoassay(RIA) (AChRAb ≥ 1 nmol/l); if available, historical data on AChR Ab levels over the last 2 years will be collected in the study records Patient may use corticosteroid treatment, equivalent to a daily dose of 30 mg prednisone or lower and stable (dose +/ mg) during the 3 months before participation Patient may use one immunosuppressive drug with or without concomitant use of corticosteroid, providing that the dosage has been stable/unchanged for 3 months before participation Blood pressure and heart rate (supine & standing) within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator Venous access sufficient to allow blood sampling as per the protocol Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures MG patients of Grade 4 or 5 based on myasthenia gravis foundation of America (MGFA) classification Patients with history or presence of a primary or recurrent malignant disease including the presence or history of a thymoma Thymectomy planned during part A of the study period or performed within 1 year prior to the first dose of study vaccine Any confirmed or suspected immunosuppressive or immunodeficient condition not related to the treatment of MG, including human immunodeficiency virus (HIV) infection, or a family history of congenital or hereditary immunodeficiency History or evidence of administration of immunoglobulins and/or any blood products within 3 months prior to the first dose of study vaccine or a planned administration of immunoglobulins during the first 3 months of the trial History or evidence of rituximab treatment within 6 months prior to first dose of study vaccine History or evidence of plasmapheresis within 3 months prior to the first dose of study vaccine or a planned plasmapheresis during the first 3 months of the trial At high risk for aspiration Pulmonary: forced vital capacity reduced to less than 70% of predicted capacity History of severe allergic disease or reactions likely to be exacerbated by any component of the vaccine | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 16.0-70.0, Melanoma Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation. 2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI. 3. Patients must have received at least one prior therapy for metastatic melanoma. 4. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. 5. Greater than or equal to 16 years of age and less than or equal to 70 years of age. 6. All participants and/or their parents or legally authorized representatives must sign a written informed consent. Assent will be obtained for all participants under the age of 18 years. 7. All participants greater than or equal to 18 years of age or older must be willing to sign a durable power of attorney 8. Clinical performance status of ECOG 0 or 1. 9. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment. 10. Serology Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.) Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. 11. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. 12. Hematology Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim WBC greater than or equal to 3000/mm3 Platelet count greater than or equal to 100,000/mm3 Hemoglobin > 8.0 g/dl 13. Chemistry Serum ALT/AST less than or equal to 2.5 times the upper limit of normal Serum Creatinine less than or equal to 1.6 mg/dl Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert s Syndrome who musthave a total bilirubin less than 3.0 mg/dl. 14. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). (Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less) 15. Patients must demonstrate progressive disease at the time of treatment. (Note: Patients who have received tyrosine kinase inhibitors (e.g. vemurafinib) may be treated if they present with stable disease at the time of treatment). 16. Subjects must be co-enrolled in protocol 03-C-0277 Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 3. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities). 4. Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses. 5. History of major organ autoimmune disease 6. Concurrent systemic steroid therapy. 7. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 8. Grade 3 or 4 Major organ Immune-related Adverse Events (IRAEs) following treatment with anti PD-1/PD-L1. 9. History of coronary revascularization or ischemic symptoms. 10. Documented LVEF of less than or equal to 45%; note: testing is required in patients with Age greater than or equal to 65 years old Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain. 11. Documented FEV1 less than or equal to 60% predicted tested in patients with A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years) Symptoms of respiratory dysfunction 12. Patients who are receiving any other investigational agents | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 8.0-999.0, Uveitis (NOT TO COVID Participants will be eligible if they: 1. Have a diagnosis of uveitis, scleritis or a disease known to be associated with intraocular inflammation, (e.g., sarcoidosis, Behcet's disease, multiple sclerosis (MS) and lymphoma) OR could serve as an unaffected control. 2. Are eight years of age or older if an affected participant. 3. Are 18 years of age or older if serving as an unaffected control. 4. For participants 18 years of age and older Are willing to give informed consent that includes collection and study of at least one peripheral blood sample (NOT TO COVID Participants will not be eligible if they: 1. Are unable to understand and sign the informed consent form. 2. Are unable or unwilling to give informed consent that includes use of medical records and clinical samples for current and future research related to vision and diseases affecting the eyes. 3. Have a systemic disease that compromises the ability to provide adequate ophthalmologic examination or treatment as determined by the investigator. 4. For participants with uveitis Have inactive anterior uveitis or quiescent infectious uveitis not requiring such regimented and intensive standardized testing as determined by the Investigator Have end stage or chronic quiescent changes in the setting of an established infectious etiology, such as an old ocular toxoplasma scar (participants with active intraocular inflammation due to infection will be recruited). The requirements for this protocol are intended to be broadly inclusive, but those individuals screened at the NEI and found to be ineligible may be evaluated under the NEI Screening Protocol for potential participation in other studies. FOR COVID-19 Participants with COVID-19 will be eligible if they: 1. Have a diagnosis of COVID-19 confirmed by a nasaopharyngeal swab (or another confirmative test) within less than or equal to 3 days prior, with symptoms of any severity. 2. Are able to give verbal consent. 3. Are 16 years of age or older FOR COVID-19 Participants with COVID-19 will not be eligible if they: 1. Use regular prescription eye drops on the day of sampling. 2. Current use of antiviral medications | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Multiple Myeloma Multiple Myeloma in Relapse Refractory Multiple Myeloma Participants with multiple myeloma who experienced disease progression after the most recent treatment regimen. Patients must have had prior treatment with a proteasome inhibitor, immunomodulatory drug, and if eligible for transplant an autologous transplant Patients must have measurable disease, defined as 1 or more of the following serum M-protein > 0.5 g/dL. For patients with IgA myeloma where the M-protein cannot be quantified on SPEP, total IgA > 0.5 g/dL Urine M-protein > 200mg/24h serum FLC assay: involved FLC level > 10 mg/dL with abnormal FLC ratio Greater than or equal to 18 years in age ECOG performance status ≤2 (see Appendix A) Life expectancy of greater than 3 months Participants must have normal organ and marrow function as defined below leukocytes ≥2,000/mcL Participants who have had chemotherapy or radiotherapy within 14 days (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 14 days earlier. The use of steroids up the equivalent of 160 mg of dexamethasone is allowed within 14 days of screening, but the last dose has to be given at least 1 day prior to initiation of treatment Participants who are receiving any other investigational agents Uncontrolled hypertension. This is defined as sustained blood pressure elevation > 140/90 despite antihypertensive therapy. Patients are allowed to start antihypertensive therapy to meet criteria; however they have to be on a stable antihypertensive regimen for at least 7 days Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because GO-203-2c is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GO_203-2c, breastfeeding should be discontinued if the mother is treated with GO-203-2c. These potential risks may also apply to other agents used in this study Individuals with a history of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin Hypersensitivity to bortezomib, boron or mannitol Grade 3 or 4 peripheral neuropathy Prior discontinuation of a bortezomib-based therapy due to toxicity attributed to bortezomib Use of G-CSF administration within 7 days of screening | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Neuroendocrine Tumors Subjects must meet all of the following to be included in this study: 1. Subjects must have histologically confirmed diagnosis of one of the following advanced/metastatic neuroendocrine tumor types: 1. WHO Classification G1/G2 (Ki67<20% and mitotic count ≤20 mitoses x 10 HPF) pancreatic neuroendocrine tumor 2. WHO Classification G1/G2 (Ki67<20% and mitotic count ≤20 mitoses x 10 HPF) gastrointestinal neuroendocrine tumor (including stomach, small intestine and colorectal origins). 2. Subjects must have evidence of measurable disease meeting the following 1. At least 1 lesion of ≥ 1.0 cm in the longest diameter for a non-lymph node, or ≥ 1.5 cm in the short-axis diameter for a lymph node, which is serially measurable according to 1.1 (Appendix I) using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of ≥ 1.5 cm. 2. Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation or liver embolization must show evidence of progressive disease based on 1.1 to be deemed a target lesion. 3. Subjects must show evidence of disease progression by radiologic image techniques within 12 months (an additional month will be allowed to accommodate actual dates of performance of scans, i.e., within ≤ 13 months) prior to signing informed consent, according to 1.1 (Appendix I) 4. Subjects must meet the following criterion regarding primary tumor site: 1. Pancreatic origin: progression after a previous targeted agent (including mTOR inhibitors, such as everolimus or antiangiogenic therapies, such as sunitinib, sorafenib, axitinib, bevacizumab within others). Combination therapies in the same treatment line (such as sorafenib plus bevacizumab, chemotherapy plus antiangiogenic drugs) are considered one treatment line and are allowed to be included in the study. Patients must be treated with only one previous line of targeted agent(s)-based therapy. Previous therapy with somatostatin analogues and/or interferon is allowed and is not considered as a previous targeted agent therapy. 2. Gastrointestinal origin: progression after therapy with antitumoral doses of somatostatin analogs (octreotide LAR 30 mg every 28 days or Lanreotide 120 mg every 28 days) and/or interferon treatment. 5. Only for patients with pancreatic origin neuroendocrine tumors, one previous line with chemotherapy is allowed. 6. Concomitant somatostatin analogues are allowed in both cohorts during the study. 7. Patients with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for at least one month. 8. All prior chemotherapy or radiation-related toxicities must have resolved to < Grade 2 (following CTCAE V 4.03 grade levels), except alopecia and infertility. 9. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 (Appendix II). 10. Previous liver locoregional therapies, such as (chemo) embolization, radiofrequency or liver-directed (radio) embolization, or systemic peptide-receptor radionucleotide therapy are allowed if the procedure was performed at least 6 months previous the informed consent form signature. 11. Adequately controlled blood pressure with or without antihypertensive medications, defined as BP < 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit. 12. Adequate renal function defined as calculated creatinine clearance ≥ 30 mL/min per the Cockcroft and Gault formula (Appendix III). 13. Adequate bone marrow function, defined as: 1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 ×103/μL). 2. Platelets ≥ 100,000/mm3 (≥ 100 × 109/L). 3. Hemoglobin ≥ 9.0 g/dL. 14. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤ 1.5. Prophylactic low molecular weight heparin therapy is allowed. 15. Adequate liver function: 1. Bilirubin ≤ 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome. 2. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 × the ULN (≤ 5 × ULN if subject has liver metastases). 16. Males or females age ≥ 18 years at the time of informed consent. 17. All females must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta human chorionic gonadotropin (β-hCG) at the baseline visit (and/or within 72h prior to the first dose of study drug). Females of childbearing potential must agree to use a highly effective method of contraception (e.g., total sexual abstinence*, an intrauterine device, a double-barrier method such as condom + spermicide or condom + diaphragm with spermicide or have a vasectomized partner with confirmed azoospermia*) throughout the entire study period and for 30 days after study drug administration. The only subjects who will be exempt from this requirement are postmenopausal women (defined as women who have been amenorrheic for at least 12 consecutive months, in the appropriate age group, without other known or suspected primary cause) or subjects who have been sterilized surgically or who are otherwise proven sterile (i.e., bilateral tubal ligation with surgery at least 1 month prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 1 month prior to dosing). The women using oral hormonal contraceptives should add an additional barrier method as there is unknown whether lenvatinib may reduce the effectiveness of the hormonal contraceptives. All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. ** Sexual abstinence will be acceptable only when this is in line with the preferred and usual lifestyle of the subject. 18. Male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, IUD) beginning at least 1 menstrual cycle prior to starting study drug(s), throughout the entire study period, and for 30 days after the last dose of study drug, unless they are sexually abstinent or have undergone a successful vasectomy. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception, as described previously. 19. Voluntary provision of written informed consent and the willingness and ability to comply with all aspects of the protocol WHO Classification G3 neuroendocrine tumors of the pancreas and gastrointestinal tract. 2. Two or more prior lines of targeted agents-based therapy in pancreatic origin and any previous line of targeted therapy for gastrointestinal origin or any ongoing antiproliferative treatment for advanced/metastatic neuroendocrine tumors, with the exception of somatostatin analogues therapy. 3. More than one previous line of chemotherapy in pancreatic neuroendocrine tumors. 4. Previous chemotherapy in gastrointestinal neuroendocrine tumors. 5. Prior treatment with lenvatinib. 6. Subjects who have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. This does not apply to the use of somatostatin analogues for symptomatic therapy. 7. Major surgery within 3 weeks prior to the first dose of study drug. 8. Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24h will be ineligible. 9. Gastrointestinal malabsorption, or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib. 10. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina; myocardial infarction or stroke within 6 months prior to the first dose of study drug, or cardiac arrhythmia requiring medical treatment. The left ventricular ejection fraction in the echocardiogram must be of at least 50%. 11. Prolongation of QTcF interval to > 480 msec. 12. Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. Treatment with low molecular weight heparin (LMWH) is allowed. 13. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug. 14. Active infection (any infection requiring treatment). 15. Active malignancy within the past 5 years (except for definitely treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix). 16. Known intolerance or hypersensitivity to the active substance (or any of the excipients). 17. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial. 18. Females who are pregnant or breastfeeding. 19. Documented active alcohol or drug abuse. 20. Patients with a prior history of non-compliance with medical regimens | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 3.0-999.0, Lymphoma Lymphoma, Non-Hodgkin Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Prior to Cell Procurement Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form for procurement Ages 3 to 17 years of age for pediatric subjects (weight must be ≥10kg), and for adults ages ≥18 years of age Diagnosis of recurrent HL or NHL in subjects who have failed >2 prior treatment regimens. Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study. CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard. Karnofsky or Lansky score of >60% (Karnofsky for ≥16 years old and Lansky for <16 years old) Evidence of adequate organ function as defined by Hemoglobin ≥ 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment) Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert's Syndrome AST ≤ 3 × ULN Serum creatinine ≤ 1.5 × ULN For subjects <18 years old use the following table for serum creatinine requirements: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to <6 ≤0.8 ≤0.8 6 to <10 ≤1.0 ≤1.0 10 to <13 ≤1.2 ≤1.2 13 to <16 ≤1.5 ≤1.4 ≥16 and <18 ≤1.7 ≤1.4 Negative serum pregnancy test in females within 72 hours prior to procurement or documentation that the subject is post-menopausal or premenarchal. Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for >1 year. • Postmenopausal status must be confirmed with documentation of absence of menses for >1 year Prior to Cell Procurement Pregnant or lactating Tumor in a location where enlargement could cause airway obstruction Active infection with HIV, HTLV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) defined as not being well controlled on therapy. Subjects are required to have negative HIV antibody or negative HIV viral load, negative HTLV1 and 2 antibody, negative HCV antibody or viral load. Hepatitis B: Subjects who are positive for Hepatitis B Surface Antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) are excluded". Subjects who are Hepatitis B Surface Antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible. Prior to Lymphodepletion Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form. CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to lymphodepletion); Note: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard. Prior to administration of lymphodepletion Absolute neutrophil count (ANC) is > 1.0 × 109/L Platelet count > 75 × 109/L For Grade 4 neutropenia, Grade ≥3 febrile neutropenia, or Grade 4 thrombocytopenia, hold bendamustine until toxicity resolve to Grade ≤2 For WOCBP negative serum pregnancy test within 72 hours prior to lymphodepletion. Imaging results from within 7 days (30 days in subjects with cutaneous T cell lymphoma) prior to lymphodepletion. Subjects who have received bridging chemotherapy must have imaging performed at least 3 weeks after most recent therapy (imaging does not need to be repeated if it is within 7 days prior to lymphodepletion). Karnofsky or Lansky score of >60% (Karnofsky for pediatric subjects ≥16 years old and Lansky for <16 years old). Available autologous transduced activated T cells that meet the Certificate of Analysis (CofA) acceptance criteria. Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year Prior to Lymphodepletion Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion. Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion. Received chemotherapy within the previous 3 weeks prior to lymphodepletion. Subject has rapidly progressive disease, per treating oncologist's discretion. Subject is not a good candidate for CAR T cell therapy, per treating oncologist's discretion. Pregnant or lactating. Tumor in a location where enlargement could cause airway obstruction. Current use of systemic corticosteroids at doses equivalent of ≥10mg prednisone daily or its equivalent; those receiving <10mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed. For pediatric subjects, physiologic replacement hydrocortisone at doses 6-12 mg/m2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10mg prednisone per day. Inhaled steroids are allowed. Subjects on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites. See http://medicine.iupui.edu/clinpharm/ddis/ for an updated list of strong inhibitors of CYP1A2 Active infection with HIV, HTLV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) defined as not being well controlled on therapy. Subjects are required to have negative HIV antibody or negative HIV viral load, negative HTLV1 and 2 antibody, negative HCV antibody or viral load. Hepatitis B: Subjects who are positive for Hepatitis B Surface Antigen are excluded. Subjects who are Hepatitis B Surface Antigen negative but hepatitis B core Antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible if the subject has initiated an anti-HBV prophylaxis regimen prior to lymphodepletion. Prior to Infusion of Cells Evidence of adequate organ function as defined by Total bilirubin ≤1.5 × ULN, unless attributed to Gilbert's Syndrome AST ≤3 × ULN Serum creatinine ≤1.5 × ULN Pulse oximetry of >90% on room air For subjects <18 years old use following table for serum creatinine requirements: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to <6 ≤0.8 ≤0.8 6 to <10 ≤1.0 ≤1.0 10 to <13 ≤1.2 ≤1.2 13 to <16 ≤1.5 ≤1.4 ≥16 and <18 ≤1.7 ≤1.4 Karnofsky or Lansky score of >60% (Karnofsky for ≥16 years old and Lansky for <16 years old) Available autologous transduced activated T cells that meet the Certificate of Analysis (CofA) acceptance criteria. Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Carbapenem Resistant Bacteria Infection Selection for CRE and CRAB GROUP: (all must be fulfilled) Isolation of CRE or CRAB from a clinical sample (e.g., a sample obtained in the work-up of a patient with suspicion of infection; therefore, screening samples are not considered) The patient meets the for any of the following infections (see definitions below): complicated urinary tract infection, pneumonia, intraabdominal infection or bloodstream infection (if the source of infection is any of the above, the patient will be included in both groups) Patient or his/her representative sign the inform consent if requested by the local Institutional Review Board (IRB). Patients in these groups will be included until the needed sample sizes are reached The infection is considered to be polymicrobial according to standard microbiological interpretation of culture results (except for cIAI, in which polymicrobial infections are allowed) The patient was participating in a clinical trial that involved active treatment for the infections The patient was previously included in the same cohort of this study for the same organism. A single episode of CRE or CRAB per patient can be included. Patients who suffer a CRE infection could later be included in the CRAB cohort if developing a CRAB infection and vice versa Patients with do not resuscitate orders or with a life expectancy of <30 days. Selection for CSE GROUP (all must be fulfilled) Isolation of CSE from a clinical sample (e.g., a sample obtained in the work-up of a patient with suspicion of infection; therefore, screening samples are not considered) The patient meets the for any of the following infections (see definitions below): complicated urinary tract infection, pneumonia, intraabdominal infection or bloodstream infection (if the source of infection is any of the above, the patient will be included in both groups) The infection is the same as that of the index case; in case of BSI, the source of bacteraemia must be the same as the index case classified as follows: UTI, pneumonia, intraabdominal infection or any other The type of acquisition is the same as for the index CRE case (nosocomial or community) The previous length of hospitalization before the infection onset is minus 1 up to minus 3 days the previous length of hospitalization before the CRE infection date in the CRE correspondent (up to minus 7 days if the CRE case occurred after 14 days of previous stay) The patient was admitted to the same type of service as the index case (medical, surgical, ICU, neonatal Unit, paediatric ICU, general paediatric wards) | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 2.0-21.0, Glioma Patients with progressive DIPG, as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), OR an increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since diagnosis, OR the appearance of a new tumor lesion since diagnosis Please note: patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation Patients with pontine lesions that do not meet these radiographic will be eligible if there is histologic confirmation of malignant glioma WHO II-IV AGE Patients must be ≥ 2 but < 22 years of age at the time of enrollment BSA Patients must have a BSA ≥ 0.80 m2 for dose 5mg/m2 Patients must have a BSA ≥ 0.65 m2 for doses of 10mg/m2 mg/m2 Patients must have a BSA ≥ 0.50 m2 for doses of 28 mg/m2 Patients who have had > 60 Gy total radiation to the pons (e.g. patients who have received re-irradiation) Patients have had prior HDAC, DAC, HSP90 inhibitors for the treatment of their DIPG Patients have had valproic acid within 28 days prior to enrollment Patients have had prior bone marrow transplant Patients have significant acute deterioration in neurologic status in 72 hours prior to enrollment, in the opinion of the treating physician Patients have impairment of GI function or GI disease that may significantly alter the absorption of panobinostat; for example severe inflammatory bowel disease Patients have diarrhea > CTCAE grade 2 Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or results OTHER Patients have a history of any other malignancy | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 5.0-18.0, Thyroiditis Hashimoto For patients Subjects 5 to 18 years old First diagnosis of hypothyroidism due to Hashimoto's thyroiditis (high levels of serum antithyroid autoantibodies (antiTPO, anti-TgAb). For Controls Healthy individuals 5 to 18 years old BMI for age between 15th and 85th percentile (z-score between -1 and +1) For patients Presence of euthyroidsm, subclinical hypothyroidism, hyperthyroidism Pre-existing medical treatment for clinical hypothyroidism Taking other medications (eg growth hormone, corticosteroids) in the last 3 months Taking food supplements (eg omega-3 fatty acids, amino acids) in the last 3 months Concomitant endocrine, metabolic, degenerative and / or chronic diseases other than obesity (eg diabetes, hyper / hypo-cortisolemia, cardiovascular diseases, kidney diseases, myasthenia, neurological diseases, psychiatric disorders eg anorexia nervosa, cancer, anemia, celiac disease, chromosomal abnormalities eg syndrome Turner, Down, etc) Participation in any daily organized physical activity (sport), more than 1 hour per day Presence of menstrual disorders in adolescent girls Having any kind of nutrition/dietary intervention (eg weight loss diet, hypocaloric, ketogenic, low-protein diet), in the last 6 months. For Controls Presence of any form of thyroid disease | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Orbital Fractures Strabismus Patients suffering from floor fractures in Tri-Service General Hospital in past 10 years Prior ocular surgeries Multiple facial trauma or facial bone fractures | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Pregnancy,Neoplastic Complications Any pregnant woman diagnosed with cancer within 6 weeks before her last menstrual period or 6 months after her end of pregnancy either by delivery or miscarriage Women diagnosed with cancer more than 6 months after the end of a pregnancy | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Ann Arbor Stage IB Hodgkin Lymphoma Ann Arbor Stage II Hodgkin Lymphoma Ann Arbor Stage IIA Hodgkin Lymphoma Ann Arbor Stage IIB Hodgkin Lymphoma Ann Arbor Stage III Hodgkin Lymphoma Ann Arbor Stage IIIA Hodgkin Lymphoma Ann Arbor Stage IIIB Hodgkin Lymphoma Ann Arbor Stage IV Hodgkin Lymphoma Ann Arbor Stage IVA Hodgkin Lymphoma Ann Arbor Stage IVB Hodgkin Lymphoma Classic Hodgkin Lymphoma Classical Hodgkin lymphoma determined by local hematopathology review One of the following Age >= 60 years Age < 60 years but unsuitable for standard chemotherapy because of a cardiac ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine clearance >= 30 and < 60 mL/min, or refused standard chemotherapy despite efforts to convince them otherwise Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if involved field is considered radiotherapy (RT) curative Previously untreated with either chemotherapy, radiation therapy or either brentuximab vedotin or nivolumab, or another check point inhibitor Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 Absolute neutrophil count (ANC) >= 1500/mm^3, unless secondary to bone marrow involvement; obtained =< 7 days prior to registration Leukocytes >= 3,000/mm^3, obtained =< 7 days prior to registration Platelet count >= 100,000/mm^3, obtained =< 7 days prior to registration Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Active, known or suspected autoimmune disease; note: subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications =< 14 days of registration; Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease Immunocompromised patients, patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy, patients with a prior history of known or suspected autoimmune disease, active hepatitis B virus surface antigen (HBV sAg+), active hepatitis C (if antibody [Ab]+ then polymerase chain reaction [PCR]+) indicating acute or chronic infection, and/or history of interstitial lung disease Allergy to brentuximab vedotin and/or nivolumab 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 | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-80.0, Myasthenia Gravis Patients between18 to 80 years of age, diagnosed with MG (see below) who have worsening myasthenic symptoms (defined as increasing diplopia, ptosis, dysarthria, dysphagia, difficulty chewing, or limb weakness severe enough to warrant immunoglobulin therapy MG diagnosis will be based upon the clinical evaluation by a neuromuscular expert and meeting any two of the following supportive 1. Abnormal Tensilon test 2. Abnormal repetitive nerve stimulation studies 3. Abnormal single fiber electromyography (EMG) 4. Increased serum acetylcholine receptor or anti-MuSK antibodies 5. Prior response to immunotherapy Respiratory distress requiring ICU admission or a vital capacity <1 L 2. Severe swallowing difficulties with a high risk of aspiration 3. Change in corticosteroid dosage in the 4 weeks prior to screening 4. Known immunoglobulin A (IgA) deficiency 5. Pregnant or breast feeding women 6. Active renal or hepatic insufficiency, clinically significant cardiac disease 7. Patients with worsening weakness associated with an infectious process 8. Previous lack of responsiveness to IVIG 9. History of previous MG crises | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 3.0-18.0, Sickle Cell Disease SCD patients who are 3-18 years old. 2. SCD (HbSS, HbSβ° thalassemia or any genotype) with at least one of the following conditions: 1. Clinically significant neurologic event (stroke) or any neurologic defect lasting > 24 hours and accompanied by an infarct on cerebral magnetic resonance imaging (MRI) 2. Minimum of two episodes of acute chest syndrome within the preceding 2-year period defined as new pulmonary alveolar consolidation involving at least one complete lung segment (associated with acute symptoms including fever, chest pain, tachypnea, wheezing, rales or cough that is not attributed to asthma or bronchiolitis) despite adequate supportive care measures 3. History of 3 or more severe pain events per year in the 2 years prior to enrollment. 3. Availability of 10/10 genotypically HLA identical related donor 4. In patients who have been treated by regular RBC transfusions >12 months, with a liver biopsy that shows no evidence of cirrhosis or active hepatitis 5. Patients must have a Karnofsky score ≥ 50 or WHO/ECOG ≥ 2 for patients age ≥ 16, Lansky score ≥ 50 for patients age < 16. 6. Adequate cardiac function: shortening fraction of > 25% or ejection fraction of > 55% by echocardiogram 7. Adequate renal function: serum creatinine within normal limits or creatinine clearance >70 ml/min/1.73 m2 8. Adequate liver function: Total bilirubin within normal limits and AST/ALT <2.5x upper limit of normal Patients with symptomatic cardiac insufficiency or arrhythmia. 2. Patients with cirrhosis on liver biopsy. 3. Hepatitis B, hepatitis C, or HIV seropositive patients. 4. Patients with other disease that would increase toxicity of transplant | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 40.0-80.0, Multiple System Atrophy (MSA) Neurogenic Orthostatic Hypotension (defined by a reduction of ≥30 mmHg drop in SBP within 3 minutes of standing, associated with impaired autonomic reflexes as assessed by autonomic function tests Pregnancy or breastfeeding Hypersensitivity to atomoxetine (severe allergic reaction, rash, urticaria, anaphylaxis) Use of other norepinephrine transporter inhibitors such as Wellbutrin (Bupropion), Cymbalta (Duloxetine), Effexor (venlafaxine), Pristiq (desvenlafaxine), Savella (milnacipran) Previous history (within 14 days prior to enrollment) and current use of monoamine oxidase inhibitors Concomitant use of strong CYP2D6 inhibitors such as delavirdine, paroxetine, fluoxetine, quinidine Pre-existing sustained severe hypertension (BP 140/80 mmhg in the sitting position) Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >2 x upper limit of normal range) Impaired renal function (serum creatinine equal or more than 1.6 mg/dl) Myocardial infarction within 6 months prior to enrollment Congestive heart failure (LV hypertrophy acceptable) | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Cto, Acef Score Among the 2952 patients with STEMI successful treatment by PCI, 395 patients (13.4%) had a non-IRA CTO lesion. 18 patients were excluded from current study as they death within 7 days (n=6) or were not to follow-up (n=7). Due to unavailability of ejection fraction or renal function before CTO-PCI, ACEF score could not be calculated in 5 patients. The remaining 377 patients (95.4%) were finally analyzed in the study. 279 patients performed a staged CTO-PCI attempt(ranging 7-28 days) and was successful in 221 of them. Due to low possibility of PCI success or patients refused to perform PCI, 98 patients did not undergo the PCI attempt. The patients were then divided into successful CTO-PCI group (221 patients) and failed/ non-attempted CTO-PCI group (156 patients). - | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-55.0, Hypertriglyceridemia Male or female (non-childbearing potential) Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening Non-smoker Medically healthy with no clinically significant laboratory profiles, vital signs or ECGs mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study History or presence of myopathy and/or hypothyroidism History or presence of transaminase elevations History or presence of hypersensitivity or idiosyncratic reaction to rosuvastatin, to other HMG-CoA reductase inhibitors, to Epanova™, to Vascepa®, or to related compounds Known sensitivity or allergy to soybeans, fish, and/or shellfish Has consumed fish within 7 days prior to check-in Female subjects who are pregnant or lactating Positive urine drug and alcohol results at screening or check-in Positive urine cotinine at screening and check-in Use of any drugs known to be inducers of CYP enzymes and/or P-gp | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 15.0-50.0, Fetal Distress Stillbirth Birth Asphyxia Acidosis Gestational Age ≥ 37 weeks Singleton gestation Cephalic presentation First stage of labor Fetal distress diagnosed in the labor ward by either FHR >160 or <110, and/or grade 2-3 meconium-stained liquor Chorioamnionitis Known fetal anomaly Antepartum hemorrhage Eclampsia Other maternal/fetal factors precluding vaginal delivery | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 2.0-30.0, Adrenal Cortex Carcinoma Alveolar Soft Part Sarcoma Central Nervous System Neoplasm Childhood Clear Cell Sarcoma of Soft Parts Clear Cell Sarcoma of Soft Tissue Ewing Sarcoma Hepatoblastoma Hepatocellular Carcinoma Osteosarcoma Recurrent Adrenal Cortex Carcinoma Recurrent Alveolar Soft Part Sarcoma Recurrent Ewing Sarcoma Recurrent Hepatoblastoma Recurrent Hepatocellular Carcinoma Recurrent Malignant Solid Neoplasm Recurrent Osteosarcoma Recurrent Primary Malignant Central Nervous System Neoplasm Recurrent Renal Cell Carcinoma Recurrent Rhabdomyosarcoma Recurrent Soft Tissue Sarcoma Recurrent Thyroid Gland Medullary Carcinoma Refractory Ewing Sarcoma Refractory Malignant Solid Neoplasm Refractory Osteosarcoma Refractory Primary Malignant Central Nervous System Neoplasm Refractory Rhabdomyosarcoma Refractory Soft Tissue Sarcoma Renal Cell Carcinoma Rhabdomyosarcoma Solid Neoplasm Thyroid Gland Medullary Carcinoma Wilms Tumor Upper age limit of =< 18 years of age for medullary thyroid carcinoma (MTC), renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) Patients must have a body surface area >= 0.35 m^2 Patients must have recurrent or refractory disease, or newly diagnosed disease with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse Ewing sarcoma Rhabdomyosarcoma (RMS) Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear cell sarcoma [CCS]) Osteosarcoma Wilms tumor Rare tumors Medullary thyroid carcinoma (MTC) Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use two methods of birth control a medically accepted barrier method of contraceptive method (e.g., male or female condom) and a second effective method of birth control-during protocol therapy and for at least 4 months after the last dose of XL184; abstinence is an acceptable method of birth control Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim) Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid Previous treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib, crizotinib) Patients who are currently receiving another investigational drug are not eligible Patients who are currently receiving other anti-cancer agents are not eligible Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin, and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) are prohibited | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Neoplasm, Trophoblastic Gestational Trophoblastic Disease Hydatidiform Mole Hydatidiform Mole, Invasive Patients are eligible if they have a histologically proven trophoblastic disease, or a diagnosis of gestational trophoblastic neoplasia done on an abnormal evolution of hCG none | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis years of age or older Clinical Diagnosis of MG with supporting evidence either from antibody testing, repetitive nerve stimulations study (RNS) or Single Fiber Electromyography (EMG) (SFEMG) Significant medical condition that would make participation in diagnostic and research part of evaluation impossible or risky. Acute or unstable medical condition Inability to provide informed consent, either directly or via appointed power of attorney Unwillingness to consent for collection of biological samples or their cryopreservation Unable to provide evidence of previous antibody testing or neurophysiology confirming the diagnosis of Myasthenia Gravis Any bleeding disorder that would prevent or present any danger during blood extraction | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 12.0-18.0, Diabetes Mellitus, Type 1 Families living in areas with high access to medical care Age:12-18 years old having diagnosed with T1DM for longer than 2 years Head injuries Epileptic episodes Psychiatric medications Lack of Hebrew abilities Disagreement to keep with all study requests History of more than one episode of severe hypoglycemic event in the past including loss of consciousness or more than one episode of diabetic ketoacidosis Patients with significant renal or liver function abnormalities | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 12.0-999.0, Spinal Muscular Atrophy SMA Kugelberg-Welander Disease A clinical diagnosis of SMA type 2, 3a, 3b or 4 Genetically confirmed homozygous SMN1 deletion Ability to complete visits during trial period Given oral and written informed consent when ≥18 years old Given informed consent by the parents or legal representative(s) in case of patients aged ≥12 till <18 years old (in accordance with Dutch law) Ability of performing at least 2 subsequent rounds of the Nine Hole Peg test A maximum total Motor Function Measure (MFM) score of 80% (i.e.: a maximum score under 80% of the D1+D2+D3 subscores) Known concomitant disorders of the NMJ (e.g. but not limited to: Lambert Eaton myasthenic syndrome, myasthenia gravis) Use of drugs that may alter NMJ function Classic SMA type 1 Apprehension against participation in EMG Inability to meet study visits Mechanical gastro-intestinal, urinary or biliary obstruction Clinical significant alterations of laboratory tests (electrolytes, liver function, kidney function, thyroid function or blood dysplasia) drawn within 14 days prior to start of study entry ECG abnormalities known as a contraindication for pyridostigmine use Current pregnancy or breast-feeding Allergy to bromides | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Generalized Myasthenia Gravis Patients with oculobulbar, bulbar or generalized MG ≥ 18 years of age and with onset of generalized symptoms or neurophysiological detection of generalized disease not more than 12 months ago. 2. The diagnosis of MG should be determined with the following: Clinical neurological status with motor symptoms consistent with MG and at least two of the following: a positive serologic test for anti-acetylcholine receptor antibody (AChR) and/or b. typical MG findings on neurophysiological testing of neuromuscular transmission with single fiber electromyography (SFEMG) and / or repetitive nerve stimulation (RNS), and / or c. Positive anti-choline esterase-test, e.g. edrophoniumchloride or improvement of MG symptoms with oral cholinesterase inhibitors as judged by the treating physician. 3. MGFA Class II to IV at screening. 4. Quantitative MG score ≥ 6 at screening 5. Women of childbearing potential must have a negative pregnancy test. 6. Patients must have provided written informed consent. 7. Patients must be able and willing to comply with all study procedures Weakness only affecting ocular or periocular muscles (MGFA Class I). 2. MG crisis at screening (MGFA Class V) 3. Thymectomy already carried out. In order to avoid difficulties to evaluate the effect of the study drug, thymectomy, where it is indicated, should be scheduled to the follow-up period, ie after the first 24 weeks. 4. Strong suspicion of thymoma, where thymectomy as judged by the treating physician should be done within 24 weeks. 5. Active malignancy, if not adequately treated 6. Pregnancy or breast-feeding. 7. Ongoing acute or chronic viral or systemic bacterial infections including HIV, latent hepatitis B, which is clinically significant, according to the study doctor's opinion and not treated with appropriate antibiotic / antiviral drugs. 8. Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease 9. Previous use of immunosuppressive drugs, including rituximab, except prednisolone at a dose of up to 40mg daily for less than 3 months. This does not apply to treatment with immunosuppressive drugs / corticosteroids (except rituximab) for other indications than MG, provided at least 12 months have passed since treatment was terminated. 10. Suspected hypersensitivity to the study drug 11. Participation in another trial of study drug within 30 days prior to screening. 12. Any medical condition which, according to the study physician's opinion, may interfere with the patient's participation in the study, poses additional risks for the patient, or that complicate the assessment of patients. 13. Vaccination within 4 weeks before inclusion | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 3.0-21.0, Diffuse Intrinsic Pontine Glioma Glioma Diffuse Midline Glioma, H3 K27M-Mutant Stratum A: • Newly diagnosed children (3-21 years old) with DIPG who are positive for the H3.3K27M mutation (positive testing in CLIA laboratory) that underwent standard radiation therapy Stratum B Newly diagnosed children (3-21 years old) with diagnosis of glioma other than DIPG who are positive for the H3.3K27M mutation (positive testing in CLIA laboratory) including spinal cord gliomas that underwent standard radiation therapy Stratum C • Newly diagnosed children 3-21 years of age with diagnosis of DIPG or midline glioma other than DIPG (excluding spinal cord gliomas) who are positive for the H3.3K27M mutation (positive testing from a CLIA or equivalent laboratory required), that underwent standard radiation therapy. The following apply to strata A, B and C The patient must test positive for HLA-A*02:01 (positive testing from a CLIA or equivalent laboratory required; only the HLA A*02:01 subtype is eligible; other subtypes are excluded) The patient must be either off systemic steroids or be on stable dose of dexamethasone (max 0.1 mg/kg/day; maximum 4mg/day) at time of enrollment Patients must not have received any prior chemotherapy, immunotherapy or bone marrow transplant for the treatment of their tumor. Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg/m^2/dose continuously during radiation therapy for 42 days) or dexamethasone is allowed Patients must have undergone radiation therapy and surgery as part of their standard of care. o Stratum A: Radiation therapy must have started within 4 weeks of diagnosis by imaging or surgery, whichever is later. o Stratum B: For subjects undergoing surgery for more extensive resection, radiation therapy should be started within 4-6 weeks from surgery. o Stratum C: Radiation therapy must have started within 4 weeks of diagnosis by imaging or surgery, whichever is later. For subjects undergoing surgery for more extensive resection, radiation therapy should be started within 4-6 weeks from surgery H3.3K27 mutation must have been confirmed in the tumor tissue in a CLIA or equivalent approved laboratory Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age (See Appendix A). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score Investigational Drugs Patients who are currently receiving another investigational drug are not eligible Prior treatment with another investigational drug Anti-cancer Agents Patients who are currently receiving other anti-cancer agents are not eligible Prior treatment with other anti-cancer agents Patients who have received a live / attenuated vaccine within 30 days of first treatment Patients with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible. Note: Patients that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair Patients with a ≥ Grade 2 hypothyroidism due to history of autoimmunity are not eligible. (Note: Hypothyroidism due to previous irradiation or thyroidectomy will not impact eligibility) Patients who have received prior solid organ or bone marrow transplantation are not eligible | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis Have the 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 study protocol procedures (including required study visits). 2. Male or female patients aged ≥18 years. 3. Diagnosis of autoimmune MG with generalized muscle weakness meeting the clinical for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II, III, or IVa, and likely not in need of a respirator for the duration of the study as judged by the Investigator. The confirmation of the diagnosis should be documented and supported by Positive serologic test for anti-AChR antibodies before Screening and at least 1 of the following 3 tests: (i) History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation or (ii) History of positive edrophonium chloride test, or (iii) Patient has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician. 4. A total score of ≥ 5 on the MG ADL at Screening and Baseline with more than 50% of this score attributed to non ocular items. 5. Patients are required to be on a stable dose of their MG treatment prior to randomization. For patients receiving AZA, other NSIDs, steroids, and/or cholinesterase inhibitors as concomitant medications the following conditions will apply AZA: treatment initiated at least 12 months ago and no dose changes in the last 6 months before screening Other NSIDs (e.g., methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide) treatment initiated at least 6 months ago and no dose changes in the last 3 months before Screening Steroids treatment initiated at least 3 months prior to and no dose changes in the last month before Screening Cholinesterase inhibitors: to be on a stable dose for >2 weeks before Screening. Note: cholinesterase inhibitors must be held for at least 12 hours consistent with the revised manual for the QMG test as recommended by the Myasthenia Gravis Foundation of America Inc (MGFA), before the MGQoL15r, MG-ADL, QMG, and MGC assessments. 6. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Visit 1 prior to administration of IMP. Female of childbearing potential are defined as all female participants unless they are postmenopausal (defined by continuous amenorrhea) for at least 2 years with a Follicle stimulating hormone (FSH) > 40 IU/L or are surgically sterile (i.e., who had a hysterectomy, bilateral oophorectomy, or have current documented tubal ligation or any other permanent female sterilization procedure). Determination of FSH levels can be used to confirm postmenopausal status in amenorrheic patients not on hormonal replacement therapy if the test result is within the postmenopausal range per the central laboratory. 7. Female participants of childbearing potential must agree to use a highly effective method of contraception (i.e., pregnancy rate of less than 1% per year) during the study and for 90 days after the discontinuation of the IMP. Adequate contraceptive methods combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS), true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female participant who is not of childbearing potential. Female participants and female partners of male study participants using a hormonal contraceptive must also use a barrier method (i.e., condom or occlusive cap [diaphragm or cervical/vault caps]) and should have been stable on their hormonal contraceptive treatment for at least 4 weeks before Screening. 8. Sterilized male patients who have had vasectomy with documented aspermia post procedure can be included. In addition, male patients must be advised not to donate sperm during this period from signing of Informed Consent Form (ICF), throughout the duration of the study, and for 90 days after the last administration of IMP. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective method of double barrier contraception (e.g., condom with spermicidal cream or jelly, 1 hormonal plus 1 barrier method or 2 simultaneous barrier methods). Male patients practicing true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) can be included Females who are pregnant or lactating. 2. MGFA Class I, IVb, and V. 3. Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Screening; or history of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Patients must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies, and a negative QuantiFERON®-TB Gold test at Screening. Patients with an indeterminate QuantiFERON®-TB Gold test result will be allowed one retest; if not negative on retesting, the patient will be excluded. 4. At Screening, have clinically significant laboratory abnormalities or as below Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN) Total serum bilirubin of > 1.5 x ULN (except for Grade 1 hyperbilirubinemia solely due to a medical diagnosis of Gilbert's syndrome) Serum creatinine > 1.5 mg/dL and creatinine clearance < 50 ml/min (using the Chronic Kidney Disease Epidemiology [CKD-EPI]-Creatinine formula) Clinically Significant proteinuria (i.e., > 3 x ULN) Hemoglobin ≤ 9 g/L Thyroid stimulating hormone or thyroglobulin outside of the central laboratory normal range International normalized ratio (INR) or activated partial thromboplastin time (aPTT) > 1.2 x ULN Total immunoglobulin G level < 6 g/L. 5. Body Mass Index (BMI) at Screening ≥ 35 kg/m2. 6. Use of rituximab, belimumab, eculizumab or any monoclonal antibody for immunomodulation within 6 months prior to first dosing. Patients with prior exposure to rituximab must have CD19 counts within the normal range per the central laboratory at Screening. 7. Use of any biological therapy or investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) before Screening. 8. Immunoglobulins given by IV (IVIg), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening. 9. Have known autoimmune disease other than MG that would interfere with the course and conduct of the study (such as uncontrolled thyroid disease or severe RA). 10. Have received vaccinations within 4 weeks before Screening or have any vaccinations planned during the study. 11. Have a history of malignancy, including malignant thymoma, or myeloproliferative or lymphoproliferative disorders at any time, unless deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before Screening. Patients with completely excised nonmelanoma skin cancers (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time. 12. Have a history of cerebrovascular accident or myocardial infarction within the last 12 months before Screening, or current severe/unstable angina, arrhythmia, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV, or uncontrolled hypertension. 13. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, or infectious diseases) which, in the opinion of the Investigator, could confound the results of the study or put the patient at undue risk. 14. Major past surgery (e.g., heart valve replacement, hip replacement) that, in the opinion of the Investigator, poses a risk to patient's safety or interferes with the study evaluation, procedures or completion. 15. Thymectomy when performed < 3 months prior to Screening. 16. History or presence of alcoholism or drug/chemical/substance abuse within 2 years before Screening per Investigator's opinion | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-100.0, Valvular Heart Disease Stenosis and Regurgitation (Diagnosis) Presence of aortic stenosis, mitral or aortic regurgitation at the time of an echocardiography at the "Cliniques Universitaires Saint Luc" | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Gastric Cancer Sentinel Lymph Node Early Gastric Cancer All patients who are deemed healthy enough to withstand laparoscopic or open anatomic gastrectomy with extended regional (D2) lymphadenectomy will be eligible. Patients much have biopsy-proven, single lesion, <4cm gastric adenocarcinoma, of stage cT1/T2/T3 N0 M0 Not able to withstand anatomical gastric resection with D2 lymphadenectomy, patient refusal, N+ve disease on pre-op work up, disease progression before surgery | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis, Ocular Informed Consent as documented by signature Patients with diplopia and/or ptosis suspicious for myasthenia gravis Vestibular disorders Significant systemic myasthenia symptoms (respiration or swallowing difficulties) unable to undergo oVEMP testing Patients with significant cardiac or respiratory disease will be excluded from the Tensilon test as part of the reference standard Women who are pregnant or breast feeding | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 16.0-85.0, Myasthenia Gravis Able to comprehend and willing to sign an Informed Consent Form (ICF) Male or female 16 to 85 years of age Diagnosis of Myasthenia Gravis History of inadequate response to conventional MG treatment Clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator Female patients of childbearing potential who are not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the course of the study, and are using contraceptive drugs or devices to prevent pregnancy during their participation in the study Willing to cooperate with study requirements, including visits to the study site every 2 months Subject's MG is responding adequately to conventional immunosuppressive treatment Subject has had no previous trial of other immunosuppressive agents Subject has a history of Chronic Obstructive Pulmonary Disease (COPD) Subject is impaired, incapacitated or incapable of completing study-related assessments Subject has the presence at screening of any severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic or cerebral disease, whether or not related to MG that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in the study Female subject has a history of breast cancer screening that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded by additional clinical, laboratory or other diagnostic evaluations Subject has a history of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ Subject currently abuses drugs or alcohol Subject has evidence of active or latent bacterial or viral infections, including positive infectious disease laboratory test result (Hepatitis B, Hepatitis C or HIV) Subject has history of herpes zoster or cytomegalovirus (CMV) infection that resolved less than 2 months prior to screening visit | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-100.0, Thyroid Eye Disease All GO patients with a GO history of at least 10 years who came for a follow-up visit in our GO clinic over a period of 5 consecutive years None | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 4.0-17.0, Epilepsy Subject is male or female, 4 to < 18 y at enrollment, and weighs at least 11 kg at Screening and on the first day of ESL dosing. 2. The informed consent must be signed by the parent or legal guardian, and, when appropriate and/or required by state or local law, minor subjects must give written informed assent prior to participation in the study. All subjects in the United States (US) must have a parent or legal guardian, sign a Health Insurance Portability and Accountability Act (HIPAA) form. 3. Confirmed diagnosis of epilepsy with partial onset seizures as defined in the Classification of Seizures of the International League Against Epilepsy: 1. Epilepsy with partial onset seizures with observable motor component, or complex partial seizures, with or without secondary generalization 2. Documented EEG recording without generalized epileptiform abnormalities and with demonstrated focal abnormalities (done within 5 years prior to screening) 4. Documented magnetic resonance imaging (MRI) scan conducted within 5 years (older scans may be acceptable with consent of Medical Monitor) prior to screening, showing either normal results or static focal abnormalities. 5. Documented seizure frequency of at least 6 seizures per month prior to screening as reported by a caregiver and documented in subject's seizure history. Note: Retrospective reporting of seizure frequency does not require diary documentation. 6. Stable treatment with 1 to 3 AEDs (excluding carbamazepine and oxcarbazepine) for ≥ 2 weeks prior to screening and at least 4 weeks prior to the first ESL dose. Vagal nerve stimulation (if present) does not count as an AED. 7. Subject and/or caregiver are willing and able to complete a daily seizure diary for the duration of the study and comply with study procedures. 8. A female subject is eligible to enter and participate in the study if she is of: 1. Non-childbearing potential because she is premenarchal (as assessed by physical examination) and < 7 y; or 2. Non-childbearing potential because she is premenarchal (as assessed by physical examination), ≥ 7 y, and has a negative urine pregnancy test at screening; or 3. Childbearing potential; has a negative serum pregnancy test at screening and agrees to satisfy one of the following requirements: • Complete abstinence from intercourse as a component of a habitually abstinent lifestyle; a minimum of 4 weeks prior to administration of the first dose of study drug, throughout the treatment period, and for a minimum of 8 weeks after completion or premature discontinuation from the study drug (abstinence must be part of an established abstinent lifestyle), and agrees to use a double-barrier method if she becomes sexually active; or • Established use of acceptable methods of contraception; a minimum of 4 weeks prior to administration of the first dose of study drug, throughout the treatment period, and for a minimum of 8 weeks after completion or premature discontinuation from the study drug. Acceptable methods of birth control are those with established failure rates of < 1%per year and Double barrier birth control, which is limited to a condom plus spermicide or a condom plus diaphragm Intrauterine device (IUD). Note: Female subjects who are ≥ 7 y and premenarchal will not routinely undergo serum pregnancy tests and will only be administered a urine pregnancy test. A positive urine pregnancy test should be confirmed by a serum test in these subjects regardless of weight. Female subjects who are < 7 y will not undergo a serum or a urine pregnancy test. Note: ESL may interfere with the action of hormonal contraceptive and therefore hormonal contraceptives are not sufficient for this protocol. 9. Males must be willing to remain sexually abstinent (consistent with lifestyle) or use an effective method of birth control (eg, male using condom and female using diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 7 days after the last dose of study drug has been taken. 10. Stable environment with caregiver who can assist in completion of seizure diary and other study assessments, if needed. 11. Subject and/or caregiver must read and write and possess an educational level and degree of understanding of the local language at a level sufficient to complete study related assessments or communicate suitably with the Investigator and study coordinator. For subjects who do not meet this criterion, a caregiver must be able to meet this requirement on the subject's behalf. for Monotherapy Conversion Subjects (at or after Month 6) 1. Subject is < 18 years-old at time of taper/conversion. 2. Subject has a satisfactory response to ESL at ≥ 6months of treatment in present study (based on tolerability and reduction in seizures, as determined by the Investigator). 3. Subject is receiving 1 or 2 background AEDs (not including benzodiazepine or barbiturate). 4. Subject does not have history of status epilepticus in the previous 3 years Subject has had prior exposure to or previously participated in a clinical study with ESL. 2. Subject has a history of allergic reaction to oxcarbazepine or carbamazepine, or a history of serious allergic reaction (Stevens Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] or similar) to any AED, or a history of serious allergic reactions to other medications. 3. Subject has had an EEG showing generalized discharges. 4. Subject has had any of the following seizure types at any time: myoclonic, absence, or atonic. 5. Subject has Lennox-Gastaut Syndrome or other secondary generalized epilepsy (including inborn errors of metabolism), or Benign Rolandic Epilepsy. 6. Subject has a current diagnosis or a history of psychogenic seizures. 7. Subject has current seizures related to an acute medical illness. 8. Subject has purely subjective seizures. 9. Subject has had status epilepticus while taking any seizure medicine in the 3 years prior to screening. 10. Subject should not have had febrile illness ≤ 2 weeks prior to screening. 11. Subject is currently taking more than 3 AEDs or is taking carbamazepine or oxcarbazepine. 12. Subject is taking any protocol-prohibited medication within 4 weeks of first ESL dose. 13. Subject has any confounding factor such as pseudoseizures or syncope. 14. Subject has a known progressive structural CNS lesion(s) or progressive encephalopathy. 15. Subject (≥ 6 y) has an active suicidal plan or intent (in the Investigator's opinion) in the past 4 weeks prior to screening. 16. Subject has a history of suicide attempt in the last 2 years prior to screening. 17. Subject is at imminent risk of suicidal or homicidal action (in the Investigator's opinion). 18. Subjects who meet the Diagnostic and Statistical Manual of Mental Disorders, 5th edition text revision (DSM-V-TR) defined for major depressive episode (MDE) within the last 6 months. Subjects with mild, chronic depression without recent hospitalization who are being maintained on a stable dose of a single antidepressant are acceptable. 19. Subject has a significant psychiatric disorder or history of recurrent episodes of severe depression requiring pharmacologic treatment or hospitalization within 2 years prior to screening. 20. Subject has a history of alcohol or substance abuse within 2 years prior to screening for study participation, or subjects currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner, which, in the opinion of the Investigator, indicates abuse. Subjects who are regular users of medical marijuana are excluded; use during participation is prohibited. 21. Subject has a positive urine drug screen (UDS) at screening. Note: Subjects with a positive drug screen for amphetamines, opiates, or benzodiazepines, who have a prescribed medication for at least 4 weeks prior to screening, may be eligible to participate in the study upon approval from the Medical Monitor. 22. Subject has a major medical illness other than epilepsy that would prevent safe participation in this study, at the discretion of the Investigator, such as (but not limited to) chronic liver or kidney impairment. 23. Subject has a disorder or history of a condition that may interfere with drug absorption, distribution, metabolism, or excretion (eg, malabsorption, gastrointestinal surgery, clinically significant abnormality of the hepatic or renal system). Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Monitor should be consulted. Subject has a history or presence of abnormal ECG, which in the Investigator's opinion is clinically significant or QTcB of ~ 450 msec per screening central over read ECG. 25. Subject is known to have tested seropositive for the human immunodeficiency virus (HIV). 26. Subject has a positive history for the hepatitis B surface antigen or hepatitis C antibody. 27. Subject has a history of hypothyroidism, hyperthyroidism, or has values for thyroid testing (free T3, free T4, thyroid stimulating hormone [TSH]) indicating the presence of significant thyroid dysfunction. 28. Subjects has the following abnormal laboratory tests (not limited to, but including the following): a. Aspartate aminotransferase (ALT)/alanine aminotransferase (AST) > 1.5 times the upper limit of normal (ULN) b. White blood cell (WBC) count of < 2500 cells/μL c. Platelet count of < 100 × 103 cells/μL Note: Subjects with stable platelet counts over the last 3 months prior to screening in the range of 80 × 103 to 100 × 103 cells/μL are eligible to participate in the study. d. Subjects have estimated creatinine clearance by modified Schwartz GFR of 77.8 mL/min/1.73m2. e. Subject has a sodium level of < 130 mEq/L. Note: If any laboratory are outside the normal range, the necessity for a repeat test should be discussed with the Medical Monitor. If upon retesting the value remains outside the protocol-specified range, the significance of this value may be discussed with the Medical Monitor for enrollment consideration. 29. Subject has difficulty providing blood samples due to poor venous access or cannot safely provide a sufficient quantity of blood. 30. Subjects of Asian ancestry must not be carriers of HLA b*1502. Either: a) subjects/caregivers must give written informed consent for genotyping, and test negative, or b) subjects/caregivers must provide documentation of prior testing confirming non carrier status and documented in subject's medical history. 31. Subject is a female who is currently breastfeeding or intending to breastfeed during the study period, or within 3 months postpartum at the time of signing informed consent. 32. Subject has participated in any investigational study within 30 days prior to screening, as documented in subject's medical history. 33. Subject is unable to comply with study visit schedules or study procedures, except those that can be performed by a caregiver. 34. Subject is a Clinical or Investigational Site staff member or relative of a staff member. 35. Subject has experienced significant blood loss within 60 days or has donated plasma within 72 hours prior to Visit 1 or intends to donate blood or undergo elective surgery during the study or within 60 days following the study | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 3.0-18.0, Type 1 Diabetes Mellitus Diabetic Ketoacidosis New onset T1D and known T1D DKA (mild, moderate and severe DKA eligible) 17 years of age Toilet trained Boys and girls All ethnicities Initial presentation to Children's Hospital Colorado (CHCO) Main ED Non-T1D etiology History of chronic kidney disease (eGFR <60ml/min/1.73m2) or dialysis dependent History of tubulopathy (e.g. Fanconi syndrome) Currently menstruating Patient visiting Colorado with plan to establish diabetes care outside of Colorado On ACE-inhibitors or angiotensin II-receptor blockers (ARB) On sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Parkinson Disease Parkinson disease or Parkinsonism (characteristic symptoms such as rigidity, extrapyramidal symptoms), with functional disorders in upper extremities and minor problems at daily activities Level 2-3 in the Hoehn and Yahr Scale Any communicable disease Severe vision impairment | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis Patients with Myasthenia Gravis Age ≥18 years N/A | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 1.0-21.0, Advanced Malignant Solid Neoplasm Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma Low Grade Glioma Malignant Glioma Recurrent Childhood Ependymoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Medulloblastoma Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Recurrent Osteosarcoma Recurrent Primary Central Nervous System Neoplasm Refractory Langerhans Cell Histiocytosis Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Primary Central Nervous System Neoplasm Rhabdoid Tumor Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Wilms Tumor Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to molecular analysis for therapy choice (MATCH) to APEC1621B based on the presence of an actionable mutation Patients must have a body surface area >= 0.53 m^2 at enrollment Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice Note: The following do not qualify as measurable disease Malignant fluid collections (e.g., ascites, pleural effusions) Bone marrow infiltration except that detected by MIBG scan for neuroblastoma Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma Elevated tumor markers in plasma or cerebrospinal fluid (CSF) Previously radiated lesions that have not demonstrated clear progression post radiation Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation in Solid Tumors (RECIST) 1.1 Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method, while receiving study treatment and for 3 months after the last dose of JNJ-42756493 (erdafitinib); male subjects (with a partner of child-bearing potential) must use a condom with spermicide when sexually active and must not donate sperm from the first dose of study drug until 5 months after the last dose of study drug Concomitant medications Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid Investigational drugs: patients who are currently receiving another investigational drug are not eligible Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed CYP2C9 agents: patients who are currently receiving drugs that are moderate to strong inducers or inhibitor of CYP2C9 are not eligible P-glycoprotein: patients who are currently receiving drugs that are potent inhibitors of p-glycoprotein are not eligible Patients who have an uncontrolled infection are not eligible | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 1.0-21.0, Advanced Malignant Solid Neoplasm Ann Arbor Stage III Non-Hodgkin Lymphoma Ann Arbor Stage IV Non-Hodgkin Lymphoma Malignant Glioma Recurrent Ependymoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Germ Cell Tumor Recurrent Malignant Solid Neoplasm Recurrent Medulloblastoma Recurrent Neuroblastoma Recurrent Non-Hodgkin Lymphoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Recurrent Primary Central Nervous System Neoplasm Recurrent Rhabdomyosarcoma Recurrent Soft Tissue Sarcoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Germ Cell Tumor Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Primary Central Nervous System Neoplasm Rhabdoid Tumor Stage III Osteosarcoma AJCC v7 Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Osteosarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Stage IVA Osteosarcoma AJCC v7 Stage IVB Osteosarcoma AJCC v7 Wilms Tumor Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621D based on the presence of an actionable mutation; note that treatment assignment may be to primary cohort A for patients with TSC1 or TSC2 loss of function mutations, primary cohort B for patients with other PI3K/MTOR pathway mutations, a histology specific biomarker positive expansion cohort if the to open such a cohort are met, or a biomarker negative expansion cohort if the to open such a cohort are met Patients accruing to dose level 1 must have a body surface area >= 0.52 m^2 at the time of study enrollment; patients accruing to dose level 2 must have a body surface area >= 0.37 m^2 at the time of study enrollment; patients accruing to dose level -1 must have a body surface area >= 0.75 m^2 at the time of study enrollment Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice Note: The following do not qualify as measurable disease Malignant fluid collections (e.g., ascites, pleural effusions) Bone marrow infiltration except that detected by MIBG scan for neuroblastoma Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma Elevated tumor markers in plasma or cerebrospinal fluid (CSF) Previously radiated lesions that have not demonstrated clear progression post radiation Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation in Solid Tumors (RECIST) 1.1 Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while receiving study treatment and for 3 months after the last dose of LY3023414 Concomitant medications Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid Investigational drugs: patients who are currently receiving another investigational drug are not eligible Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial Patients who have an uncontrolled infection are not eligible Patients who have insulin dependent diabetes are not eligible Patients who have received a prior solid organ transplantation are not eligible Patients with subependymal giant cell astrocytomas (SEGAs) are not eligible | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Thrombotic Microangiopathies Patients be scheduled to undergo HSCT; 2. Not received decitabine 6 month ago; 3. Without severe organ damage; 4. ECOG 0-2; 5. Informed consent were obtained Be sensitive to NAC; 2. Bronchial asthma； 3. Peptic ulcer； 4. Severe organ damage； 5. Pregnancy and breastfeeding women； | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Pulmonary Hypertension Systemic Sclerosis Mixed Connective Tissue Disease Heart Failure With Normal Ejection Fraction Healthy Diagnosis of pulmonary hypertension and followed at the Comprehensive Pulmonary Hypertension Center OR Diagnosis of systemic sclerosis and followed at the Comprehensive Pulmonary Hypertension Center OR Diagnosis of mixed connective tissue disease and followed at the Comprehensive Pulmonary Hypertension Center OR Undergoing outpatient right heart catheterization Age<18 Pregnant Unable to understand English Currently incarcerated Unwilling or unable to sign informed consent | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-75.0, B Cell Lymphoma B Cell Leukemia Myeloma Hepatocellular Carcinoma Pancreatic Carcinoma Adenocarcinoma of Esophagogastric Junction I. B-Cell Lymphoblastic Leukaemia/Lymphoma 1. Patients aged between 18 ~ 65 with B-cell lymphoblastic leukaemia/lymphoma. 2. CD19-positive B-cell lymphoblastic leukaemia/lymphoma. 3. Patients with unmet medical needs for which there are no effective therapies known at this time: A. Relapsed or Refractory (r/r) Acute Lymphoblastic Leukemia (ALL) Patients with r/r ALL for whom hematopoietic stem cell transplantation (HSCT) is not suitable due to following reasons: 1. Age; 2. Excessive tumor burden or concomitant disease; 3. No donor available. B. CD19-positive Follicular Lymphoma: 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy; 2. Less than 6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months); 3. Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.). C. Chronic Lymphocytic Leukemia (CLL) 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy); 2. Less than6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months); 3. Not eligible or appropriate for conventional HSCT. 4. Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.). D. Mantle Cell Lymphoma 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy); 2. Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.)； 3. Relapsed after prior autologous SCT. E. B-Cell Prolymphocytic Leukemia (PLL) Relapsed or residual disease after at least 1 prior therapy and not eligible for HSCT. F. CD19-positive Diffuse Large B Cell Lymphoma 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy; 2. Stage III-IV disease. 3. Less than 6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months); 4. Disease progression after most recent therapy (chemotherapy, MoAb, etc.). 4. Expected survival > 12 weeks. 5. At least one measurable lesion (≥ 10 mm) for patients with lymphoma. 6. ECOG scores 0-1, or KPS scores > 70. 7. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis. 8. WBC ≥ 2.5×10^9/L; PLT ≥ 60×10^9/L (for patients with lymphoma); Hb ≥ 9.0 g/dL; LY ≥ 0.47×10^9/L; LY% ≥ 15%. 9. Serum Alb ≥ 30 g/L. 10. Serum creatinine ≤ 1.5 ULN. 11. ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN. 12. Serum total bilirubin ≤ 1.5 ULN. The above lab results should not those obtained from continuous supportive treatment that is ongoing. II. Myeloma 1. Patients aged between 18 ~ 75 with relapsed or refractory multiple myeloma. 2. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 3. Patients with relapsed or refractory malignancies who meet the following descriptions: 1. Curative efficacy is little or disease progressed after 2 courses of standard treatment regimen; 2. Disease relapsed after chemotherapy or HSCT. Curative efficacy is little or disease progressed after 2 courses of original treatment regimen; 3. More than 30 days between last treatment and disease progression; 4. There is no indication for HSCT at present; 5. Disease progression is defined as per "Chinese Guidelines for Diagnosis and Treatment of Multiple Myeloma (Version 2015)". One or more of the following conditions should be met: i. Serum M-protein increases ≥ 25% (absolute increase should be ≥ 5 g/L). If serum M protein is ≥ 50 g/L at baseline, increase of serum M protein can be ≥ 10 g/L; ii. Urine M-protein increases ≥ 25% (absolute increase should be ≥ 200 mg/24 h); iii. If the serum and urine M-protein are not detectable, a ≥ 25% increase in the difference between involved and uninvolved FLC levels is required (absolute increase should be ≥ 100 mg/L); iv. Bone marrow plasma cell percentage increases ≥ 25% (absolute increase should be ≥ 10%); v. Size of existing bone lesions or soft tissue plasmacytomas increased by ≥ 25%, or development of new lytic bone lesions or oft tissue plasmacytomas; vi. Development of hypercalcemia that can be attributed to plasma cell proliferative disorder (corrected calcium is > 2.8 mmol/L or 11.5 mg/dL). 4. Expected survival > 12 weeks. 5. Disease is measurable, and at least one of the following conditions should be satisfied: 1. Serum M-protein is ≥ 10 g/L; 2. 24-hour urine M-protein is ≥ 200 mg; 3. Serum FLC is ≥ 5 mg/dL; 4. Plasmacytomas that can be measured or evaluated by imaging; 5. Bone marrow plasma cell percentage is ≥ 20%. 6. ECOG scores 0 or CCI scores ≤ 2. 7. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis. 8. WBC ≥ 1.5×10^9/L; PLT ≥ 45×10^9/L; Hb ≥ 9.0 g/dL. 9. Serum creatinine ≤ 1.5 ULN. 10. ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN. The above lab results should not those obtained from continuous supportive treatment that is ongoing. III. Hepatocellular Carcinoma (HCC) 1. Patients aged 18 ~ 70 with refractory hepatocellular carcinoma. 2. Patients with HCC that cannot be eradicated by resection who have received ablation or resection in the last 4 to 12 weeks. 3. IHC testing confirmed as GPC3-positive HCC. 4. Expected survival > 12 weeks. 5. At least one measurable lesion (≥ 10 mm). 6. Cirrhosis of the liver: Child-Pugh Class A, or Child-Pugh Class B scored at 7. 7. ECOG scores 0 or KPS scores > 70. 8. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis. 9. Hematology: WBC ≥ 2.5×10^9/L; PLT ≥ 60×10^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.0×10^9/L; LY ≥ 0.4×10^9/L. 10. Blood Chemistry: Serum Alb ≥ 30 g/L; Serum lipase and serum amylase < 1.5 ULN; Serum creatinine ≤ 1.5 ULN; ALT ≤ 5 ULN; AST ≤ 5 ULN; Serum total bilirubin ≤ 2.5 ULN. 11. Coagulation Test: Prothrombin time is at most 4 seconds longer than normal value. 12. Able to understand and sign the informed consent. All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment. IV. Pancreatic Carcinoma and Adenocarcinoma of Esophagogastric Junction 1. Patients aged 18 ~ 70 with pathologically confirmed advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction. 2. IHC testing confirmed as Claudin18.2 positive. 3. Patients with advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction that cannot be eradicated by resection. 4. Expected survival after first dose of study drug > 12 weeks. 5. At least one measurable lesion (≥ 10 mm) available for imaging assessment. 6. ECOG scores 0 7. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis. 8. WBC ≥ 2.5×10^9/L; PLT ≥ 100×10^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.5×10^9/L; LY ≥ 0.47×10^9/L; LY% ≥ 15%. 9. Serum Alb ≥ 30 g/L. 10. Serum lipase and serum amylase < 1.5 ULN. 11. Serum creatinine ≤ 1.5 ULN. 12. ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN; If osseous metastasis or liver metastasis is developed and alkaline phosphatase is > 2.5 ULN, than ALT and AST should be < 1.5 ULN. 13. Serum total bilirubin ≤ 1.5 ULN. 14. PT: INR < 1.7; PT < (ULN + 4) s All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment Patients with any of the following conditions are not eligible for this study. 1. Transduction of target lymphocytes < 10%, expansion in response to αCD3/CD28 costimulation < 5-fold. 2. Pregnant or lactating women. 3. HIV positive, or HCV positive 4. Uncontrolled active infection, including active tuberculosis and HBV DNA copies ≥ 1×10^3 copies/mL. 5. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. 6. Allergic to immunotherapies and related drugs. 7. Patients with heart disease for which treatment is needed or with poorly controlled hypertension. 8. Hyponatremia: serum sodium level < 125 mmol/L. 9. Baseline serum potassium < 3.5 mmol/L (taking potassium supplements before participating in the study to raise potassium level is acceptable). 10. Previous treatment with chemoradiotherapy, immunotherapy and tumor-targeting drug conducted 2 weeks prior to participation in this study or blood collection. 11. Patients have undertaken immunosuppressor for graft-versus-host disease (GVHD) within 4 weeks before participation in this study or blood collection, or the patient is diagnosed with acute or chronic GVHD. 12. Other severe disease that may restrain patients from participating in this study (e.g. diabetes, severe cardiac dysfunction, myocardial infarction or unstable arrhythmias or unstable angina in recent 6 months, gastric ulcer, active autoimmune disease, etc.) | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis, Generalized Willing and able to provide written informed consent after the nature of the study has been explained and before the start of any research-related procedures. 2. Male or female ≥18 years of age. 3. Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as confirmed at Screening or by previous antibody test, with report available. 4. Confirmatory EMG or EMG report. 5. Myasthenia Gravis Foundation of America (MGFA) Class II to IV at Screening. 6. MG-ADL score of ≥6 at Screening, with more than 50% of this score attributed to non-ocular items. 7. Patients receiving steroids or pyridostigmine should not have any modification of drug regimen during the month before Screening. 8. Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin [HCG] at screening); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment. 9. Ability to participate in the study based on overall health of the patient and disease prognosis, as applicable, in the opinion of the Investigator; and able to comply with all requirements of the protocol, including completion of study questionnaires Epilepsy and currently on medication. 2. Concomitant use of medicinal products with a known potential to cause QTc prolongation. 3. Patients with long QT syndromes. 4. History of thymectomy within 12 months before Screening. 5. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator. 6. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study. 7. Patients receiving immunomodulatory treatment (e.g. plasma exchange [PE], therapeutic plasma exchange [TPE], intravenous immunoglobulin G [IVIG]) should not have any treatment in the previous 4 weeks prior to Randomization or at any time during the study. 8. Use of rituximab or other similar biologic medications for immunomodulation within 6 months prior to Screening. 9. Treatment with an investigational drug (other than amifampridine) or device within 30 days before Screening or while participating in this study. 10. Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confound the assessment of the patient. 11. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s) | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-85.0, Generalized Myasthenia Gravis Diagnosis of gMG [Myasthenia Gravis Foundation of America (MGFA) Class II-IVa] at Screening Positive serology for acetylcholine receptor (AChR) autoantibodies QMG score ≥ 12 at Screening and Randomization No change in corticosteroid dose for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period No change in immunosuppressive therapy, including dose, for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period Thymectomy within 6 months prior to Randomization or scheduled to occur during the 12 week Treatment Period History of meningococcal disease Current or recent systemic infection within 2 weeks prior to Randomization or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Randomization | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 8.0-65.0, Acute Leukemia High-risk acute myelogenous leukemia or acute lymphocytic leukemia based on clinical and biological characteristics, which including but not limited to poor response to induction therapy and relapse or beyond second remission. 2. Karnofsky performance status (KPS) >= 70% 3. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately 4. All candidates for this study must have a prepared allogeneic stem cell donor, including human leukocyte antigen matched or partially mismatched donor 5. A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan (MUGA) or echocardiogram 6. Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance >70 ml/min 7. Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN) 8. Pulmonary function: Carbon Monoxide Diffusing Capacity corrected (DLCOcorr) > 50% of normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained) 9. The time from the end last induction or re-induction attempt should be greater than or equal to 14 days 10. All subjects must have the ability to understand and the willingness to sign a written informed consent Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months 2. Evidence of Human immunodeficiency virus (HIV) infection 3. Prior myeloablative transplant within the last 6 months 4. Prior radiation therapy that would the use of TMLI 5. Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Cancer of Pancreas Pancreas Cancer Pancreatic Adenocarcinoma Pancreatic Cancer Pancreatic Neoplasms Patient must be able to understand and willing to sign a written informed consent document Age greater than of equal to 18 years. Because no dosing or adverse event data are currently available on the use of M7824 in combination with gemcitabine in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials Histologically or cytologically proven pancreatic adenocarcinoma (subjects with endocrine or acinar pancreatic carcinoma are not eligible) Patients must have disease that is not amenable to potentially curative resection Subjects must have progressed on or after standard first-line systemic chemotherapy ECOG performance status of 0 to 1 Must have evaluable or measurable disease per 1.1 Adequate hematological function defined by white blood cell (WBC) count greater than or equal to 3x10(9)/L with absolute neutrophil count (ANC) greater than or equal to 1.5x10(9)/L Patients who are receiving any other investigational agents Prior therapy with any antibody / drug targeting T cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody Anticancer treatment within designated period before enrollment including minor surgical procedure (such as biliary stenting) within 14 days major surgical procedure or radiation treatment within 28 days chemotherapy or experimental drug treatment with published half-life known to be 72 hours within 14 days experimental drug treatment with unpublished or half-life greater than 72 hours within 28 days radiotherapy for measurable lesions delivered in a normal organ-sparing technique within 21 days (except for palliative radiotherapy) Concurrent treatment with non-permitted drugs including herbal remedies with immunostimulating properties (for example, mistletoe extract) or known to potentially interfere with major organ function (for example, hypericin) Previous malignant disease (other than the target malignancy to be investigated in this trial) within the last 3 years. Subjects with a history of cervical carcinoma in situ, superficial or no-invasive bladder cancer, or basal cell or squamous cell carcinoma in situ previously treated with curative intent are NOT excluded | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 3.0-17.0, Influenza, Human Male or female age 3 to 17 years History of two previous influenza immunizations at any time, or influenza infection during the previous year Female subjects of child-bearing potential (as defined by the onset of menses) must agree to prevent pregnancy and usage of an effective contraception, or having practiced sexual abstinence for at least 28 day prior to the first study vaccine administration. Female subjects of child-bearing potential must be tested for pregnancy within 24 hours prior to vaccine administration In good general health, healthy or medically stable, as determined by the medical history, physical examination and the Investigator's judgment Parent(s) or legal representative of each potential subject must comprehend the study requirements, sign the informed consent before any procedure, and agree to comply with planned study procedures and visits. Provide written consent prior to enrollment and initiation of any study procedure Pediatric consent will be attained as per the Research Ethics Committee's determination when subject is aged 8 or older Known allergy to eggs (anaphylaxis, angioedema, respiratory distress), severe allergy (e.g. anaphylaxis) to other components of the vaccine or contraindications to receive the comparator IIV4 Use of systemic steroids at doses of 2mg/kg/day for more than 10 days of prednisone or its equivalent. (The use of nasal or topical steroids will be allowed) Active neoplastic disease or a history of any malignancy History of receiving the influenza vaccine within the previous 6 months Plan to receive another influenza vaccine, during the study term History of receiving immunoglobulin or another blood product within the 3 months prior to enrollment in this study Acute or chronic medical condition that, in the opinion of the Investigator, would render immunization unsafe or would interfere with the evaluation of efficacy or the immune response to the vaccine An acute illness, including a body temperature greater than 37.7°C, within 3 days prior to immunization Receive an experimental vaccine or medication within 1 month prior to enrollment in this study, or the expectation to receive an experimental vaccine, medication, or blood product during the study period Developmental delay, neurologic disorder, or seizure disorder requiring ongoing medical assistance (note: history of febrile seizure is not considered an criterion) | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Myasthenia Gravis Associated With Thymoma myasthenia gravis patients after thymectomy not extubation | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 9.0-26.0, Prevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in Situ Not pregnant and 1) not a woman of childbearing potential (WOCBP), or 2) a WOCBP who has not had sex with males or has had sex with males and used effective contraception since the first day of participant's last menstrual period through Day 1 and understands and agrees that during the study she should not have sexual intercourse with males without effective contraception (the rhythm method, withdrawal, and emergency contraception are not acceptable methods per the protocol) Participant and participant's parent or guardian (participants aged 9-17 years only) provided written informed consent/assent Provided a primary and alternative telephone for follow-up purposes Extension Stage: participant was enrolled in the 9-19 years old group, received 3 doses of V501 in the Base Stage, and participant and participant's legally acceptable representative (if applicable) provided written informed consent/assent for the study extension History of severe allergic reaction that required medical intervention Allergic to any vaccine component, including aluminum, yeast, or Benzonase® (nuclease) Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections Currently immunocompromised or was diagnosed as having congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition History of splenectomy Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives History of recent or ongoing alcohol or other drug abuse History of a positive test for HPV Any history of abnormal Pap test History of external genital wart, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), vulvar cancer or vaginal cancer | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Ulcerative Colitis in Remission Ultrasound Relapse/Recurrence A confirmed diagnosis of ulcerative colitis Six-point Mayo score ≤ 1 Two consecutive faecal calprotectin tests <200 mg/kilogram Male or non-pregnant, non-nursing female ->18 years of age at Patients treated for minimum 1 year with first-line anti-tumor necrosis factor (TNF) treatment in sustained clinical remission during the last 3 months Subject capable of understanding and signing an informed consent form Discontinuation of systemic 5-acetylsalicylic acid (ASA) or immunomodulatory therapy or other medication that could affect disease activity during the last 3 months prior to randomization Any treatment of systemic corticosteroids due to disease exacerbation during the last 3 months (i.e. patients being in steroid free clinical remission Patients on anti-TNF monotherapy with intolerance to both 5-ASA and immunomodulatory therapy Change in the anti-TNF treatment during the last 3 months due to disease related factors, not including dose/frequency adjustments due to drug concentration measurements Use of any second-line anti-TNF medication irrespective of reason for stopping first-line anti-TNF Previous failed attempts of anti-TNF discontinuation of more than 4 months' duration, with the exception of discontinuation due to pregnancy Detection of anti-TNF antibodies in moderate-high titers prior to randomization Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible Pregnancy Breastfeeding | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Von Willebrand Disease Historically lowest VWF:Ag and/or VWF:RCo and/or VWF:CB ≤ 0.30 IU/mL and/or FVIII:C ≤ 0.40 IU/mL Treatment at a Hemophilia treatment center in the Netherlands All types of VWD All ages Other known bleeding disorders present | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Metastatic Malignant Solid Neoplasm Patients with biopsy-proven metastatic solid tumor and be eligible to receive nivolumab per standard of care Patients will be allowed to have any number of prior lines of therapy for metastatic cancer Patients with measurable and non-measurable disease are allowed to participate Absolute neutrophil count (ANC) ? 1.5 x 10^3/mm^3 Hemoglobin (Hgb) ? 9 g/dL Platelet count ? 100 x10^3/mm^3 Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ? 2.5 x upper limit of normal (ULN) or ? 5 x ULN in patients with liver metastases Prothrombin time ? 1.5 x ULN Total bilirubin ? 1.5 x ULN (unconjugated bilirubin of < 3 x ULN for patients with known Gilbert syndrome) Creatinine clearance of ? 50 ml/min by Cockcroft-Gault equation History of prior therapy with ibrutinib or nivolumab Unable to swallow capsules or having disease that is significantly affecting gastrointestinal function and/or inhibiting small intestine absorption Diagnosis of congenital or acquired immunodeficiency with the exception of chemotherapy induced immune suppression Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids of greater than or equal to prednisone 10 mg/day or other immunosuppressive agents; patients with history of adequately treated Hashimoto?s thyroiditis will be eligible; patients requiring a short course of a high dose prednisone burst to treat asthma or common obstructive pulmonary disease will also be eligible 5 days following completion of the prednisone treatment Use of systemic steroids at a dose above 10 mg/day of prednisone or prednisone equivalent in cycle 1 of study therapy; systemic steroids must be discontinued at least 5 days prior to initiating study therapy; exception will be given to patients who develop immune related adverse events that necessitate use of steroids or other immune suppressive agents; following cycle 1 of study treatment, the use of systemic steroids will be allowed per discretion of the treating physician Active, non-infectious pneumonitis Ongoing or active infection requiring systemic therapy History of being positive for human immunodeficiency virus (HIV) History of hepatitis B or C History of receiving live vaccine within 30 days of planned start of study therapy | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 15.0-45.0, Anemia, Iron Deficiency Age 15-45 years old at intake Confirmed intrauterine pregnancy by 1st trimester ultrasound Antepartum iron supplementation, other than prenatal vitamins Placental abruption or hemorrhage Initial visit >20 weeks gestation Diagnosis of sickle cell disease or thalassemia Diagnosed with anemia at initial prenatal visit Diagnosis of autoimmune issues that could effect iron levels | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, Myasthenia Gravis, MuSK Participated in the MSK-002 study Epilepsy and currently on medication Clinically significant abnormalities in ECG, in the opinion of the Investigator | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Transplant;Failure,Kidney Kidney transplant recipients. Taking tacrolimus Unable to consent | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 2.0-17.0, Anisometropia Hyperopia High Myopia Amblyopia Isometropic Amblyopia Bilateral High Astigmatism Criteria Children aged 2 to 17 with significant anisometropia or isoametropia and amblyopia that have failed traditional treatment for at least 6 months Anisometropic group The anisometropia must be at least 3.00 diopters The amblyopic eye best corrected visual acuity must be at least 2 lines worse than the fellow eye in verbal children Isoametropic group Myopia must be at least -4.00 diopters in both eyes Hyperopia must be at least 4.00 diopters in both eyes Astigmatism must be at least 2.50 diopters in both eyes History of significant corneal abnormality that, in the investigator's opinion, may limit visual rehabilitation History of known collagen disorder History of known corneal ectasia History of previous herpes simplex keratitis Corneal thickness of less than 450u | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.5-18.0, Midazolam Child (boy or girl) for whom surgery under general anesthesia is scheduled Child aged 6 months to 17 years old Child with a body mass index between the 3rd and 97th percentile Child with ASA (American Society of Anesthesiology) status of I or II. Young girl of childbearing age (ie after puberty) and sexually active to have a result negative to the pregnancy test Child whose parents / legal representative (s) agree to sign a consent form Child whose opinion / agreement was / tried to be collected Child and parents / legal representative (s) being ready and able to participate in the study, understanding and undertaking to respect the study procedures throughout the duration of the study Child enrolled in a social security scheme Child with midazolam allergy, benzodiazepine hypersensitivity or hypersensitivity known to one of the excipients of the formulation of the study Child with respiratory disease (severe respiratory failure, acute respiratory depression) Child with heart disease Child with gastrointestinal disorders that may affect absorption or gastroesophageal reflux Child with growth disorders or abnormal weight-of-weight Child taking Cytochrome P450 Interactions Within 60 Days of in the study Child with kidney failure, liver failure, history of myasthenia gravis, or neurological disease Pregnant or lactating girl Child who has a known human immunodeficiency virus (HIV) infection, or active hepatitis B, or active hepatitis C A child who could present any condition that may prevent his participation in the study, according to the judgment of the investigator | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-18.0, Xlsma DMD X-ALD TSC SMA: patients meet the all the following 1. Clinically manifestation: hypotonia, progressive symmetric and proximal weakness affecting the legs more than the arms, sparing of the facial muscles but often with bulbar muscle weakness. 2. Neurogenic EMG. EMG is also usually not needed in type 1 and 2 children; this investigation can help in more chronic forms in which the phenotype might be less striking. 3. Along with EMG and NCV test, a muscle or nerve biopsy can be used to diagnose spinal muscular atrophy if molecular genetic testing of SMN1 does not identify mutations. 4. Genetic testing of SMN1/SMN2: Homozygous absence of exons 7 and 8 of the SMN1 gene(96%), or only of exon 7, or other mutations. SMN2 copy numbers may vary. Genetic testing is the gold standard of diagnosis None. - 2. DMD: patients meet the all the following 1. Clinically manifestation: weakness, clumsiness, a Gowers' sign, difficulty with stair climbing, or toe walking. developmental delay or increased concentrations of serum enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, or very high creatine kinase level. 2. Dystrophin gene mutation: dystrophin gene deletion and duplication testing is usually the first confirmatory test best done by MLPA or comparative genomic hybridisation array. Approximately 70% of individuals with DMD have a single-exon or multi-exon deletion or duplication in the dystrophin gene. If deletion or duplication testing is negative, genetic sequencing should be done to screen for the remaining types of mutations that are attributed to DMD (approximately 25-30%). 3. Muscle biopsy: if genetic testing does not confirm a clinical diagnosis of DMD, then a muscle biopsy sample should be tested for the presence of dystrophin protein by immunohistochemistry of tissue cryosections or by western blot of a muscle protein extract. Muscle samples from DMD patient has no dystrophin present, while BMD Becker muscular dystrophy (with some partially functional dystrophin present) None. - 3. X-ALD: patients meet the all the following 1. Clinically manifestation: 1. Attention deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years. 2. Adrenomyeloneuropathy (AMN) manifests as progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical function; all symptoms are progressive over decades, most commonly in an individual in his twenties or middle age. 3. Magnetic resonance imaging shows cerebral demyelination. 2. Dystrophin gene mutation: The diagnosis of X-ALD is usually established in a female proband with detection of a heterozygous ABCD1 pathogenic variant and elevated VLCFA None. - 4. TSC: criteria:patients meet the all the following A. Clinical diagnostic 1. Major features: (1) Hypomelanotic macules (≥3, at least 5-mm diameter). (2) Angiofibromas (≥3) or fibrous cephalic plaque. (3) Ungual fibromas (≥2). (4) Shagreen patch. (5) Multiple retinal hamartomas. (6) Cortical dysplasias. (7) Subependymal nodules. (8) Subependymal giant cell astrocytoma. (9) Cardiac rhabdomyoma. (10) Lymphangioleiomyomatosis (LAM). (11) Angiomyolipomas (≥2). 2. Minor features: (1)"Confetti" skin lesions. (2) Dental enamel pits (>3). (3) Intraoral fibromas (≥2). (4) Retinal achromic patch. (5) Multiple renal cysts. (6) Nonrenal hamartomas. Two major features or one major feature with ≥2 minor features can diagnose. Either one major feature or ≥2 minor features can diagnosis possibly. B. Genetic diagnostic The identification of either a TSC1 or TSC2 pathogenic mutation in DNA from normal tissue is sufficient to make a definite diagnosis of TSC None. - | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 6.0-999.0, Cystic Fibrosis-related Diabetes Age >/= 6 years 2. Diagnosis of cystic fibrosis 3. CF patients regularly attending the CF centers 4. Clinically stable in previous 3wks absence of major clinical events including pulmonary exacerbations no change in their habitual treatment regimen including introduction of antibiotics or steroids in the past 3 weeks Diagnosis of type 1 diabetes, type 2 diabetes, or MODY 2. Organ transplantation 3. new diagnosis of CFRD in the past 6 months 4. antidiabetic treatment in past 6 mos (insulin or oral hypoglycemic agents) -patients with previous CFRD diagnosis, but not currently taking insulin/glucose-lowering medications for at least 6 months should be included 5. pulmonary exacerbation associated with systemic steroid requirement in the last 6 months 6. on CFTR corrector less than 6 months prior to enrollment | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Anticoagulants Compliance, Medication confirmed diagnosis of NOACs indications, such as thromboprophylaxis for non-valvular atrial fibrillation, prevention or treatment of deep vein thrombosis/pulmonary embolism, and thromboprophylaxis after knee/hip replacement. 2. Age >18 years old, unlimited for gender. 3. Written or phoned informed consent was obtained from all patients or their families | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Acute Leukemia Acute Leukemia in Relapse Acute Myeloid Leukemia Relapsed or Refractory Acute Leukemia Research patients enrolled are those patients with relapsed or refractory CD123+ acute leukemia (Acute Myeloid Leukemia/ acute lymphoblastic leukemia ); 2. Relapsed: is defined as patients that had a first complete remission (CR) before developing recurrent disease (increased bone marrow blasts); 3. Refractory: is defined as patients that have not achieved a first CR after 2 cycles of induction chemotherapy; for patients with leukemia evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy; 4. Research participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis; CD123 positivity must be confirmed by either flow cytometry or immunohistochemistry within 90 days of study entry; cytogenetics, flow cytometry, and molecular studies (such as FMS-like tyrosine kinase-3 [FLT-3] status) will be obtained as per standard practice; 5. Karnofsky performance status score >= 70; 6. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; 7. Calculated creatinine clearance (absolute value) of >= 50 mL/minute or creatinine < 2.0 mg/dl or < 2 times upper limit of normal for the research participant's age group; 8. Serum bilirubin =< 3.0 mg/dL; 9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 times the institutional upper limits of normal; 10. Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) >= 50%; 11. Diffusion capacity of carbon monoxide (DLCO) or forced expiratory volume in one second (FEV1) > 45% predicted; 12. Research participants' last dose of prior chemotherapy or radiation must be >= 2 weeks before leukapheresis; 13. If a research participant has undergone prior allogeneic stem cell transplant, he/she must be off all immunosuppressants for graft versus host disease (GVHD) for at least 2 weeks before undergoing leukapheresis; 14. Negative serum or urine pregnancy test; 15. All research participants must have the ability to understand and willingness to sign a written informed consent or age appropriate assent for pediatric patients Acute Promyelocytic Leukemia, t(15,17) (q22;q12); 2. Pregnant and lactating women; 3. Research participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection, or poorly controlled infection; 4. History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab 5. Dependence on corticosteroids (5mg/day prednisone more than 2 weeks); 6. A known hypersensitivity to any of the test materials or related compounds; 7. Presence of active and clinically relevant Central Nervous System (CNS) disorder; 8. Undergone prior allogeneic stem cell transplant, GVHD occurred within 6 months, requiring immunosuppressive therapy; 9. Active autoimmune disease, such as psoriasis and rheumatoid arthritis; 10. Other situations the clinicians think not eligible for participation in the research | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 16.0-999.0, Thalassemia Subject Thalassemia patients with serum ferritin ≥500 μg/L Patients aged 16 and above Without blood transfusion within 1 week before admission, with hemoglobin ≥ 80 g/L Voluntarily participate in the experiment, and the process of obtaining informed consent form meeting the requirements of GCP Subject Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive Patients with history of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic multiple intestinal polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other patients whom investigators believe to have potential intestinal complications Liver dysfunction (ALT or AST > 2.5×ULN); or renal dysfunction (serum creatinine > 1.5×ULN) Uncontrolled active infections Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs Allergic constitution: allergic to or with contraindication of main ingredients or excipients of CN128 tablets (microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, silica, sodium stearate fumarate, Opadry) Patients who have abnormal ECG with clinical significance: congenital long QT syndrome or known family history of long QT syndrome; QTc > 450ms (male) or QTc > 470ms (female); patients who have ventricular or atrial tachyarrhythmia with clinical significance, etc Family planning participants (including male subjects) during or within three months after the trial Patients with a history of blood donation within 3 months before the trial Patients with a history of smoking (more than 5 cigarettes or products with equivalent nicotine per day), alcoholism (more than 14 units of alcohol per week: 1 alcohol unit equals 10 mL or 8 g pure alcohol; 25 mL 40% liquor, 330 mL 5% beer, 175 mL 12% red wine equals 1.0, 1.5, 2.0 alcohol units respectively), drug abuse and addiction history | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 10.0-50.0, Post-Traumatic Orbital Deformity Class I, II blowout floor fracture Presented within 2 weeks of trauma Have muscle or soft tissue distortion with clinically significant diplopia, enophthalmos or restrictive strabismus Comminuted orbital fractures involving the rim Associated globe injuries Delayed presentation | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 12.0-999.0, Cytomegalovirus Infections Age ≥12 years Weight ≥30 kg Transplant recipient (HCT, SOT) or other immunocompromised patients including those with HIV infection that require antiviral treatment for CMV Documented CMV disease or persistent CMV infection (CMV virus load above 500 IU/mL on consecutive measurements, at least one day apart) CMV infection is refractory to treatment (defined as ≥14 days of standard CMV treatment without clinical improvement for CMV disease, or failure to achieve >1 log reduction in CMV VL after ≥14 days of standard treatment for CMV infection)16,17 Current CMV infection has documented genotypic resistance to ganciclovir or foscarnet For patients with any prior CMV infection episode that broke through letermovir prophylaxis, but not during the current CMV infection, documentation of letermovir susceptibility testing should demonstrate absence of letermovir mutations known to confer resistance to letermovir Severe myelosuppression (ANC <1000/µL, Hemoglobin <8g/dL, or Platelets <25,000/µL)17 or renal dysfunction (estimated creatinine clearance <60 mL/min by MDRD in adults or < 60 ml/min/1.73 m2 by bedside Schwartz equation in < 18 years-old) at baseline or which develops during antiviral treatment. --Patients who develop severe myelosuppression or renal dysfunction during antiviral treatment as defined above are eligible without having to meet the refractoriness/antiviral resistance criterion Combinations of genotypic antiviral resistance and organ dysfunction that lead to are presented in the full protocol table The effects of letermovir on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of letermovir administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of letermovir administration. --Patients of childbearing potential must have a negative serum or urine pregnancy test History of allergic reactions attributed to compounds of similar chemical or biologic composition to letermovir Known history of cirrhosis with Child-Pugh Class C hepatic insufficiency at screening Acute liver injury at baseline meeting Hy's law Current CMV infection broke through letermovir prophylaxis Patients with life expectancy of less than a week. Determination of life expectancy will be discussed with the patient's primary treatment physician Patient taking strong inhibitors or inducers of hepatic CYP enzymes including rifampicin, phenytoin, clarithromycin, ritonavir, or cobicistat HIV patients who are receiving antiretroviral treatment protease inhibitors (darunavir, lopinavir, etc) whether by themselves or boosted with ritonavir or cobicistat, or HIV patients receiving cyclosporine treatment due to strong drug-drug interactions Combinations of genotypic antiviral resistance and organ dysfunction that do not meet are described in the full protocol table | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-999.0, High-Risk Resectable NSCLC Histologically proven non-small-cell lung cancer (core biopsy required) Squamous or non-squamous histology Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at The Second Affiliated Hospital Zhejiang University School of Medicine Either a formalin fixed paraffin block or a minimum of fifteen 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues, or from a new biopsy if needed Stage High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at The Second Affiliated Hospital Zhejiang University School of Medicine. This may clinical stage IA3 (≥2cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included ECOG performance status 0-1 Adequate organ function as follows Leukocytes ≥ 2,000/mm3 Absolute neutrophil count (ANC) ≥ 1000/mm3 Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen Administration of chemotherapy or any other cancer therapy in the pre-operative period Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia) Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment Subjects with a history of symptomatic interstitial lung disease Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) Known positive history or positive test for Human Immunodeficiency Virus or Acquired ImmunoDeficiency Syndrome (AIDS) History of allergy to study drug components | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-65.0, Myasthenia Gravis Being diagnosed with MG by a neurologist Aged between18-65 years To be in Stage II or III according to the Clinical Classification of the Medialia Gravis Functional Assessment (MGFA) The Mini Mental Test score should be over 24 in order to be cooperative to the physiotherapist's instructions To volunteer to participate in the study Having a cognitive problem and having a Mini Mental Test score below 24 To have had myasthenic crisis in the last month Modification of medical treatment and dose in the last month Systemic, orthopedic and neurological disease in addition to the disease Participation in physiotherapy program in the last six months | 1 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 6.0-17.0, Myasthenia Gravis Myasthenia Gravis, Juvenile Form Myasthenia Gravis, Generalized Male or female pediatric participants 6 to <18 years of age at time of assent/consent Vaccinated against Neisseria meningitidis Documented vaccination against Haemophilus influenzae and Streptococcus pneumoniae infections prior to dosing as per local and country specific immunization guidelines for the appropriate age group Diagnosis of MG confirmed by positive serologic test for anti-acetylcholine receptor antibodies at Screening, and 1 of the following: (a) history of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation; (b) history of positive anticholinesterase test (for example, edrophonium chloride or neostigmine test); or (c) participant demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors, as assessed by the Investigator Presence of refractory gMG, defined as participants with gMG who have 1 or more of the following: (a) failed treatment ≥1 year with at least 1 immunosuppressive therapies (IST), defined as follows: (1) persistent weakness with impairment of activities of daily living; (2) myasthenia gravis (MG) exacerbation and/or crisis while on treatment; or (3) intolerance to ISTs due to side effect or comorbid condition(s). (b) Require maintenance plasma exchange (PE) or intravenous immunoglobulin (IVIg) to control symptoms; and/or (c) in the opinion of the Investigator, MG poses a significant functional burden despite current MG treatment MGFA Clinical Classification of Class II to IV at Screening In patients aged 12 to 18 years, QMG total score ≥ 12 at Screening; in patients aged 6 to 11 years, no minimum QMG is required for inclusion; however, patients must have documented limb weakness in at least one limb All MG-specific treatment has been administered at a stable dosing regimen of adequate duration prior to Screening Parent or legal guardian is an Alexion employee Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before Screening History of thymectomy within 12 months prior to Screening Are pregnant or lactating Any unresolved acute, or chronic, systemic bacterial or other infection, which is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics Use of PE within 4 weeks prior to first dose Use of rituximab within 6 months prior to first dose Patients who are under 15 kg and are receiving maintenance IVIg Participation in another interventional treatment study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater Have previously received treatment with eculizumab or other complement inhibitors | 2 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Iliac Aneurysm Angiography AAA Sub-study A. scheduled endovascular aneurysm repair using the Gore IBE device Sub-study B. Patients that have been treated with an iliac branched device in the past in conjunction with either a dedicated IIA component (Gore IBE device) or non-dedicated IIA component (Cook IBD) and who are scheduled for follow-up imaging within the period July 2016-January 2017 No specific Patients will be treated according to the hospital's standard practice | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 21.0-99.0, Dry Eye Patients with dry eye symptoms, who cannot be satisfactorily managed by currently available dry eye medication 2. TBUT ≤10s 3. Presence of corneal fluorescein staining 4. Visual acuity affected by poor tear film quality 5. No contraindication for blood extraction/ plasmapheresis 6. Age between 21 to 99 years old 7. Skin lesions The skin at the site of venepuncture in the antecubital area should be free of lesions. Donors with boils, open wounds, chronic eczema or any severe skin infection must be rejected Active ocular infection. 2. Any other specified reason as determined by clinical investigator 3. Severe cardiovascular disease 4. Severe respiratory disease 5. Uncontrolled epilepsy 6. Abnormal bleeding conditions 7. Pregnancy 8. Infectious diseases Patients who are known or diagnosed to have HIV, Hepatitis B or Hepatitis C carriers should not be accepted for donation Patients who have risk factors for infectious diseases should not be accepted for donation. 9. Patients who have been or are being treated for bacteraemia, or have a significant bacterial infection that can be associated with bacteraemia. 10. Unable to come for follow up at the required frequencies and duration. This includes non-Singapore residents who are patients of the dry eye clinic. 11. In order to avoid serious infections, especially corneal keratitis, we will not patients with high risks for infection in this study, such as those patients with a persistent epithelial defect, wearing of contact lenses, previous ocular surgery such as penetrating keratoplasty or any other ocular surgery. 12. Patients with persistent epithelial defect that requires bandage contact lens | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 18.0-80.0, Latent Tuberculosis Age 18 years + 1 day (defined as date of birth plus one day). This age cutoff has been selected as tstin3d.com has only been validated for this age group. Subjects must have all of the following Untreated Latent Tuberculosis Infection (LTBI), defined as positive Tuberculin skin test/QuantiFERON TB Gold test or T-spot assay done within 1 month prior to enrollment Absence of active TB disease as determined by history, physical examination, chest X-ray, (sputum smear and/or culture done as needed by the assessing physician for Mtb) Greater than 10% cumulative risk of developing active TB disease (determined by TSTin3D.com) A subject will be excluded if any of the following are met Presence of active TB disease BMI <16 Cardiovascular instability (Blood pressure: Systolic >180 or <90 mm/Hg or Diastolic >100 or < 50mm/Hg; pulse <40 or >110) Chest X-Ray report within last 3 months not available HIV positive and currently on treatment with a regimen that has severe drug interactions with 3HP Presumed infected with INH or Rifapentine (RIF)-resistant M. tuberculosis Women who are pregnant, nursing or expect to become pregnant for the duration of the study Temperature ≥38.5°C or other clinical evidence of an acute infection at screening History of treatment for >14 consecutive days with a rifamycin or >30 consecutive days with isoniazid during the previous 2 years | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 15.0-60.0, Orbital Fractures Age group: from 15 to 60 years old Patients with blow-out fractures Patients suffering from dermatological diseases | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Oligohydramnios Pregnant women between 24-37 weeks of gestation, single fetus, who were diagnosed with an amniotic fluid index at the 5th percentile or below, according to the current gestational age No medical indication for immediate delivery Refusal to participate in the study A medical recommendation for delivery within two weeks of diagnosis Fetal malformation or proof of fetal infection that known to cause oligohydramnios (eg CMV) Premature rupture of membrane Multiple pregnancy Medical contraindication to the low-salt diet | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 0.0-999.0, Hereditary Angioedema Type I and II patients diagnosed with HAE type I and II with signed informed consent laboratory diagnostic documenting plasma levels of C1 inhibitor antigen and function and of C4 antigen patients without HAE type I and II patients without documented laboratory diagnostic patients not capable to give informed consent | 0 |
The patient is a 16-year-old girl recently diagnosed with myasthenia gravis, class IIa. She complains of diplopia and weakness affecting in her upper extremities. She had a positive anti-AChR antibody test, and her single fiber electromyography (SFEMG) was positive. She is on acetylcholinesterase inhibitor treatment combined with immunosuppressants. But she still has some symptoms. She does not smoke or use illicit drugs. She is not sexually active, and her menses are regular. Her physical exam and lab studies are not remarkable for any other abnormalities. BP: 110/75 Hgb: 11 g/dl WBC: 8000 /mm3 Plt: 300000 /ml Creatinine: 0.5 mg/dl BUN: 10 mg/dl Beta hcg: negative for pregnancy | eligible ages (years): 3.0-25.0, Dravet Syndrome Severe Myoclonic Epilepsy of Infancy diagnosed with Dravet syndrome according to the of Ceulemans and Cras (2004) aged minimum 3 years and maximum 25 years at having minimum 1 year of walking experience severe epileptic seizure (status epilepticus or tonic-clonic insult over 3 min) within the 24 hours before the assessment insufficient cooperation to perform 3D gait analysis comorbidities of other neurological and/or orthopedic disorders not linked to Dravet syndrome | 0 |
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