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
