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

NCT ID: NCT02535364

Last Updated: 2020-05-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-21
• Study Completion Date: 2017-09-01

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

JCAR015 (CD19-targeted CAR T cells)

JCAR015 was administered as two intravenous (IV) infusions separated by 14 to 28 days.

Group Type: EXPERIMENTAL

JCAR015 (CD19-targeted CAR T cells)

Intervention Type: BIOLOGICAL

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.

Interventions

JCAR015 (CD19-targeted CAR T cells)

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.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juno Therapeutics, a Subsidiary of Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nikolaus Trede, MD, PhD

Role: STUDY_DIRECTOR

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Locations

University of Alabama Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

City of Hope

Duarte, California, United States

University of California

San Francisco, California, United States

University of Colorado Denver -- Anschutz Medical Campus

Aurora, Colorado, United States

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, United States

The Blood and Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, United States

Northwestern University Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Sidney Kimmel Comprehensive Cancer Center @ Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He Q, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DC, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014 Feb 19;6(224):224ra25. doi: 10.1126/scitranslmed.3008226.

Reference Type: BACKGROUND

PMID: 24553386 (View on PubMed)

Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013 Apr;3(4):388-98. doi: 10.1158/2159-8290.CD-12-0548. Epub 2013 Apr 2.

Reference Type: BACKGROUND

PMID: 23550147 (View on PubMed)

Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, Hedvat C, Kobos R, Curran K, Steinherz P, Jurcic J, Rosenblat T, Maslak P, Frattini M, Sadelain M. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013 Mar 20;5(177):177ra38. doi: 10.1126/scitranslmed.3005930.

Reference Type: BACKGROUND

PMID: 23515080 (View on PubMed)

Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, Olszewska M, Bernal Y, Pegram H, Przybylowski M, Hollyman D, Usachenko Y, Pirraglia D, Hosey J, Santos E, Halton E, Maslak P, Scheinberg D, Jurcic J, Heaney M, Heller G, Frattini M, Sadelain M. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011 Nov 3;118(18):4817-28. doi: 10.1182/blood-2011-04-348540. Epub 2011 Aug 17.

Reference Type: BACKGROUND

PMID: 21849486 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

015001

Identifier Type: -

Identifier Source: org_study_id