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

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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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC)

Secondary Outcome

 Percentage of Participants With CR or CRi, as Determined by an IRC

Condition

Acute Lymphoblastic Leukemia

Intervention

JCAR015 (CD19-targeted CAR T cells)

Study Arms / Comparison Groups

 JCAR015 (CD19-targeted CAR T cells)
Description:  JCAR015 was administered as two intravenous (IV) infusions separated by 14 to 28 days.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

82

Start Date

August 21, 2015

Completion Date

September 1, 2017

Primary Completion Date

April 24, 2017

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Nikolaus Trede, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02535364

Organization ID

015001


Responsible Party

Sponsor

Study Sponsor

Juno Therapeutics, Inc.


Study Sponsor

Nikolaus Trede, MD, PhD, Study Director, Juno Therapeutics, Inc.


Verification Date

June 2018