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

NCT02535364 | Terminated Phase 2 Results DMC

• 1 other identifier: 015001
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 18

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

acute lymphoblastic leukemia; ALL; chimeric antigen receptor; CAR; CAR T cells; JCAR015; autologous T cell therapy; cell therapy

Outcome Measures

Primary Outcomes (1)

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

  Overall remission rate (ORR) is defined as the percentage of participants with CR or CRi based on IRC assessment. For CR, all of the following must be met: (1) in bone marrow, trilineage hematopoiesis and \< 5% blasts; (2) in peripheral blood, neutrophils \> 1,000/µL, platelets \> 100,000/µL, and circulating blasts \< 1%; (3) no clinical evidence of extramedullary disease by physical examination and no symptoms suggestive of CNS involvement (if additional assessments such as CSF assessment by lumbar puncture or Ommaya reservoir tap, CNS imaging, or biopsy are performed, results must show no evidence of disease); (4) no platelet and/or neutrophil transfusions ≤ 7 days before the date of peripheral blood sampling, and (5) no clinical evidence of recurrence for 4 weeks. For CRi, all criteria for CR are met except that one or more of the following exists in the peripheral blood: neutrophils ≤ 1,000/µL, platelets ≤ 100,000/µL, or platelet transfusions ≤ 7 days before blood sampling.

  Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion

Secondary Outcomes (21)

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

  Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion

• Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC

  Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion

• Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC

  Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion

• Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi

  Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion

• Percentage of Participants Who Achieved a MRD-Negative CR or CRi

  Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion

Study Arms (1)

JCAR015 (CD19-targeted CAR T cells)

EXPERIMENTAL

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

Biological: JCAR015 (CD19-targeted CAR T cells)

Interventions

JCAR015 (CD19-targeted CAR T cells) 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.

JCAR015 (CD19-targeted CAR T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of consent
• 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
• Morphological evidence of disease in bone marrow (at least 5% blasts)
• Evidence of CD19 expression
• Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 at the time of screening
• Adequate pulmonary, renal, hepatic, and cardiac function
• Adequate central or peripheral vascular access for leukapheresis procedure

You may not qualify if:

• Isolated extramedullary disease relapse
• Concomitant genetic syndrome or other known bone marrow failure syndrome
• Burkitt's lymphoma/leukemia or chronic myelogenous leukemia lymphoid blast crisis (p210 BCR-ABL+)
• Prior malignancy, unless treated with curative intent and with no evidence of active disease present for \> 5 years before screening
• Prior treatment with any gene therapy product
• Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
• Systemic fungal, bacterial, viral, or other infection that is not controlled, at the time of screening
• Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
• Active central nervous system (CNS) involvement by malignancy (defined as CNS-3 per National Comprehensive Cancer Network \[NCCN\] guidelines)
• 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
• 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
• Participation in an investigational research study using an investigational agent within 30 days of screening
• 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
• Pregnant or nursing women
• Use of prohibited medications:

Sponsors & Collaborators

• Juno Therapeutics, a Subsidiary of Celgene: lead

Study Sites (18)

University of Alabama Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35295, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California

San Francisco, California, 94143, United States

Location

University of Colorado Denver -- Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, 33136, United States

Location

The Blood and Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern University Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Sidney Kimmel Comprehensive Cancer Center @ Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (4)

• 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.

  PMID: 24553386 BACKGROUND

• 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.

  PMID: 23550147 BACKGROUND

• 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.

  PMID: 23515080 BACKGROUND

• 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.

  PMID: 21849486 BACKGROUND

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Nikolaus Trede
• Organization: Juno Therapeutics

Nick.Trede@junotherapeutics.com

206-566-5886

Study Officials

• Nikolaus Trede, MD, PhD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: August 28, 2015
• Study Start: August 21, 2015
• Primary Completion: April 24, 2017
• Study Completion: September 1, 2017
• Last Updated: May 4, 2020
• Results First Posted: July 19, 2018

Record last verified: 2020-04

Locations

US (18)