Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell Acute Lymphoblastic Leukemia (B-ALL)
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: JCAR015 (CD19-targeted CAR T cells)
Intervention description: Part A: Following leukapheresis and concurrent with generation of JCAR015, participants received, at the Investigator's discretion, cytoreductive chemotherapy based on the Investigator's choice of regimens and/or supportive care.
Part B: Participants who were eligible for treatment in Part B received two IV doses of JCAR015 CAR T cells separated by 14 to 28 days. JCAR015 infusion was preceded by lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: acute lymphoblastic leukemia; ALL; chimeric antigen receptor; CAR; CAR T cells; JCAR015; autologous T cell therapy; cell therapy

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.
    

Eligibility criteria:

        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