NCT02535364 - Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell Acute Lymphoblastic Leukemia (B-ALL) | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years at the time of consent 2. Relapsed or refractory B-ALL, defined as: * First or greater bone marrow relapse from CR, or * Any bone marrow relapse after allogeneic hematopoietic stem cell transplant (HSCT); subjects must be at least 100 days from HSCT at the time of screening and off immunosuppressant medication for at least 1 month at the time of screening, and have no active graft-vs-host disease (GVHD), or * Refractory B-ALL, defined by not having achieved a CR or CRi after two attempts at remission induction using standard regimens, or * Ph+ B-ALL if subjects are intolerant to or ineligible for tyrosine kinase inhibitor (TKI) therapy, or have progressed after at least one line of TKI therapy 3. Morphological evidence of disease in bone marrow (at least 5% blasts) 4. Evidence of CD19 expression 5. Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 at the time of screening 6. Adequate pulmonary, renal, hepatic, and cardiac function 7. Adequate central or peripheral vascular access for leukapheresis procedure Exclusion Criteria: 1. Isolated extramedullary disease relapse 2. Concomitant genetic syndrome or other known bone marrow failure syndrome 3. Burkitt's lymphoma/leukemia or chronic myelogenous leukemia lymphoid blast crisis (p210 BCR-ABL+) 4. Prior malignancy, unless treated with curative intent and with no evidence of active disease present for \> 5 years before screening 5. Prior treatment with any gene therapy product 6. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening 7. Systemic fungal, bacterial, viral, or other infection that is not controlled, at the time of screening 8. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening 9. Active central nervous system (CNS) involvement by malignancy (defined as CNS-3 per National Comprehensive Cancer Network \[NCCN\] guidelines) 10. History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease 11. History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis 12. Participation in an investigational research study using an investigational agent within 30 days of screening 13. History of treatment with a murine-derived biological product other than blinatumomab unless subject has been shown to be negative for human-anti-mouse-antibodies (HAMA) prior to or during screening 14. Pregnant or nursing women 15. Use of prohibited medications: 1. Steroids: Therapeutic doses of corticosteroids are prohibited within 7 days prior to leukapheresis. 2. Allogeneic cellular therapy: Donor lymphocyte infusions (DLI) are prohibited within 4 weeks prior to leukapheresis 3. GVHD therapies: Any drug used for GVHD within 4 weeks prior to leukapheresis 4. Chemotherapies: Salvage chemotherapy must be stopped at least 1 week prior to leukapheresis 16. Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis

Outcomes

Primary Outcomes

Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC)

Overall remission rate (ORR) is defined as the percentage of participants with CR or CRi based on IRC assessment. For CR, all of the following must be met: (1) in bone marrow, trilineage hematopoiesis and \< 5% blasts; (2) in peripheral blood, neutrophils \> 1,000/µL, platelets \> 100,000/µL, and circulating blasts \< 1%; (3) no clinical evidence of extramedullary disease by physical examination and no symptoms suggestive of CNS involvement (if additional assessments such as CSF assessment by lumbar puncture or Ommaya reservoir tap, CNS imaging, or biopsy are performed, results must show no evidence of disease); (4) no platelet and/or neutrophil transfusions ≤ 7 days before the date of peripheral blood sampling, and (5) no clinical evidence of recurrence for 4 weeks. For CRi, all criteria for CR are met except that one or more of the following exists in the peripheral blood: neutrophils ≤ 1,000/µL, platelets ≤ 100,000/µL, or platelet transfusions ≤ 7 days before blood sampling.