Clinical Trials /

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

NCT02535364

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell <span class="go-doc-concept go-doc-disease">Acute Lymphoblastic Leukemia</span> (B-<span class="go-doc-concept go-doc-disease">ALL</span>)

Title

  • Brief Title: Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell Acute Lymphoblastic Leukemia (B-ALL)
  • Official Title: 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
  • Clinical Trial IDs

    NCT ID: NCT02535364

    ORG ID: 015001

    Trial Conditions

    Acute Lymphoblastic Leukemia

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    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 2 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.

    Trial Arms

    Name Type Description Interventions
    JCAR015 Experimental JCAR015 will be administered as two intravenous (IV) infusions.

    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 chemotherapy 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall remission rate (ORR)

    Secondary Outcome Measures

    Duration of remission (DOR)

    Percentage of patients who achieve CR or CRi with no evidence of minimal residual disease (MRD) in the bone marrow

    Treatment-related adverse events as assessed by CTCAE v4.03

    Relapse-free survival

    Event-free survival

    Overall survival

    ORR at Month 6 following the final JCAR015 infusion

    Percentage of patients who achieve a morphologic remission within 6 months after the final JCAR015 infusion and then proceed to hematopoietic stem cell transplant (HSCT)

    Maximum concentration of JCAR015 (Cmax) in the peripheral blood and bone marrow

    Time to maximum concentration of JCAR015 (Tmax) in the peripheral blood and bone marrow

    Area under the concentration-vs-time curve (AUC) in the peripheral blood and bone marrow

    Profile of soluble immune factors that may be generated in response to JCAR015 administration

    Trial Keywords

    acute lymphoblastic leukemia

    ALL

    chimeric antigen receptor

    CAR

    CAR T cells

    JCAR015

    autologous T cell therapy

    cell therapy