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

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

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.

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.

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