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

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Juno Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02535364
First received: August 24, 2015
Last updated: November 29, 2016
Last verified: August 2016
  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.

Condition Intervention Phase
Acute Lymphoblastic Leukemia
Biological: JCAR015 (CD19-targeted CAR T cells)
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Juno Therapeutics, Inc.:

Primary Outcome Measures:
  • Overall remission rate (ORR) [ Time Frame: After 50 efficacy-evaluable subjects have received JCAR015 infusion and completed 6 months from first JCAR015 infusion or discontinued earlier ]
    Efficacy of JCAR015 therapy -- ORR, which includes complete remission (CR) and complete remission with incomplete hematopoietic recovery (CRi), as determined by assessments of bone marrow, peripheral blood, physical exam, and cerebrospinal fluid (CSF). The primary endpoint will be based on independent review committee (IRC) assessment.


Secondary Outcome Measures:
  • Duration of remission (DOR) [ Time Frame: 12 months ]
  • Percentage of patients who achieve CR or CRi with no evidence of minimal residual disease (MRD) in the bone marrow [ Time Frame: 12 months ]
  • Treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 12 months ]
  • Relapse-free survival [ Time Frame: 12 months ]
  • Event-free survival [ Time Frame: 12 months ]
  • Overall survival [ Time Frame: 12 months ]
  • ORR at Month 6 following the final JCAR015 infusion [ Time Frame: 6 months ]
  • 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) [ Time Frame: 12 months ]
  • Maximum concentration of JCAR015 (Cmax) in the peripheral blood and bone marrow [ Time Frame: 12 months ]
  • Time to maximum concentration of JCAR015 (Tmax) in the peripheral blood and bone marrow [ Time Frame: 12 months ]
  • Area under the concentration-vs-time curve (AUC) in the peripheral blood and bone marrow [ Time Frame: 12 months ]
  • Profile of soluble immune factors that may be generated in response to JCAR015 administration [ Time Frame: 12 months ]

Estimated Enrollment: 110
Study Start Date: August 2015
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JCAR015
JCAR015 will be administered as two intravenous (IV) infusions.
Biological: JCAR015 (CD19-targeted CAR T cells)

Part A: Following leukapheresis and concurrent with generation of JCAR015, participants will receive, at the Investigator's discretion, cytoreductive chemotherapy based on the Investigator's choice of regimens and/or supportive care.

Part B: Participants who are eligible for treatment in Part B will receive two IV doses of JCAR015 CAR T cells. JCAR015 infusion will be preceded by lymphodepleting chemotherapy.


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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02535364

Locations
United States, Alabama
University of Alabama Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35295
United States, California
City of Hope
Duarte, California, United States, 91010
University of California
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado Denver -- Anschutz Medical Campus
Aurora, Colorado, United States, 80045
United States, Florida
Sylvester Comprehensive Cancer Center/UMHC
Miami, Florida, United States, 33136
United States, Georgia
The Blood and Marrow Transplant Program at Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Illinois
Northwestern University Robert H Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center @ Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center
New York City, New York, United States, 10065
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Juno Therapeutics, Inc.
Investigators
Study Director: Nikolaus Trede, MD, PhD Juno Therapeutics, Inc.
  More Information

Publications:

Responsible Party: Juno Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02535364     History of Changes
Other Study ID Numbers: 015001
Study First Received: August 24, 2015
Last Updated: November 29, 2016

Keywords provided by Juno Therapeutics, Inc.:
acute lymphoblastic leukemia
ALL
chimeric antigen receptor
CAR
CAR T cells
JCAR015
autologous T cell therapy
cell therapy

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Burkitt Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma

ClinicalTrials.gov processed this record on April 21, 2017