A Phase 2, Single-arm, Multicenter Trial to Determine the Efficacy and Safety of JCAR015 in Adult Subjects With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Acute Lymphoblastic Leukemia
- Sponsor
- Juno Therapeutics, a Subsidiary of Celgene
- Enrollment
- 82
- Locations
- 18
- Primary Endpoint
- Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC)
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
This single-arm, multicenter Phase 2 trial will treat adult patients who have relapsed or refractory B-ALL with an infusion of the patient's own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to leukemia cells that express the CD19 protein on the cell surface. The study will determine if these modified T cells (called JCAR015) help the body's immune system eliminate leukemia cells. The trial will also study the safety of treatment with JCAR015, how long JCAR015 cells stay in the patient's body, the extent to which JCAR015 eliminates minimal residual disease, and the impact of this treatment on survival.
Detailed Description
This is a single-arm, multicenter Phase 2 study to determine the efficacy and safety of JCAR015 in adult patients with relapsed or refractory B-ALL. The study will have the following sequential phases: Part A (screening, leukapheresis, cell product preparation, and cytoreductive chemotherapy) and Part B (treatment and follow-up). The follow-up period for each participant is approximately 12 months after the final JCAR015 infusion. The total duration of the study is expected to be approximately 3 years. Long-term follow-up for survival, toxicity, and viral vector safety will continue under a separate long-term follow-up protocol per health regulatory authority guidelines, currently up to 15 years after the last JCAR015 infusion.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years at the time of consent
- •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
- •Morphological evidence of disease in bone marrow (at least 5% blasts)
- •Evidence of CD19 expression
- •Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 at the time of screening
- •Adequate pulmonary, renal, hepatic, and cardiac function
Exclusion Criteria
- •Isolated extramedullary disease relapse
- •Concomitant genetic syndrome or other known bone marrow failure syndrome
- •Burkitt's lymphoma/leukemia or chronic myelogenous leukemia lymphoid blast crisis (p210 BCR-ABL+)
- •Prior malignancy, unless treated with curative intent and with no evidence of active disease present for \> 5 years before screening
- •Prior treatment with any gene therapy product
- •Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- •Systemic fungal, bacterial, viral, or other infection that is not controlled, at the time of screening
- •Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
- •Active central nervous system (CNS) involvement by malignancy (defined as CNS-3 per National Comprehensive Cancer Network \[NCCN\] guidelines)
- •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
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)
Time Frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
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.
Secondary Outcomes
- Relapse-Free Survival (RFS), as Determined by an IRC(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- EFS(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Percentage of Participants With CR or CRi, as Determined by an IRC(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Percentage of Participants Who Achieved a MRD-Negative CR or CRi(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- OS(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Percentage of Participants Who Achieved a Morphologic Remission Within 6 Months After the Final JCAR015 Infusion and Then Proceeded to HSCT(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Event-Free Survival (EFS)(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Duration of Remission (DOR) as Determined by an IRC(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Flow Cytometry(Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable))
- Tmax in the Peripheral Blood as Measured by Flow Cytometry(Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable))
- RFS, as Determined by an IRC(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Overall Survival (OS)(Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion)
- Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Quantitative Polymerase Chain Reaction (qPCR)(Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable))
- Time to Maximum Concentration of JCAR015 (Tmax) in the Peripheral Blood as Measured by qPCR(Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable))
- Area Under the Concentration-vs-Time Curve (AUC) for JCAR015 in the Peripheral Blood as Measured by qPCR(Pre-dose Day 1 of the first JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion)
- Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion(Day 1 (first JCAR015 infusion) up to 6 months after the last JCAR015 infusion)
- AUC for JCAR015 in the Peripheral Blood as Measured by Flow Cytometry(Pre-dose Day 1 of the first JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion)
- Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015(Part B Screening; Day 14 after the first JCAR015 infusion; Pre-Dose Day 1 of the second JCAR015 infusion; Day 14 after the second JCAR015 infusion; and Day 28, Month 3, Month 6, and Month 12 after the last JCAR015 infusion)