Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
An Open-Label, Phase 1/2 Study of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)
2 other identifiers
interventional
320
2 countries
86
Brief Summary
This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. Another separate Phase 1 cohort will assess the combination of JCAR017 and concurrent venetoclax. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2017
Longer than P75 for phase_1
86 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 29, 2017
CompletedFirst Posted
Study publicly available on registry
November 6, 2017
CompletedStudy Start
First participant enrolled
November 27, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 26, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 26, 2027
March 4, 2026
March 1, 2026
10 years
October 29, 2017
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (10)
Phase 1 JCAR017 monotherapy arm: adverse events
Proportion of subjects experiencing adverse events
Up to 48 months post treatment
Phase 1 JCAR017 monotherapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: adverse events
Proportion of subjects experiencing adverse events
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm
Proportion of subjects who have CR after treatment with JCAR017 + ibrutinib using iwCLL 2018 guidelines
Through post treatment up to Month 48
Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: adverse events
Proportion of subjects experiencing adverse events
Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm
Proportion of subjects who have CR after treatment with JCAR017 + venetoclax using iwCLL 2018 guidelines
Through post treatment up to Month 48
Phase 2 JCAR017 monotherapy expansion arm
Proportion of subjects who have CR after treatment with JCAR017 using iwCLL 2018 guidelines
Through post treatment up to Month 48
Phase 2 JCAR017 Double exposed monotherapy expansion arm: overall response rate (ORR)
ORR defined as the rate of complete response/remission (CR) \[including complete response/remission with incomplete marrow recovery (Cri)\] plus PR \[including nodular partial response (nPR)\] based on Independent Review Committee (IRC) assessment using International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines
Up to approximately 24 months
Secondary Outcomes (48)
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: adverse events
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: laboratory abnormalities
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: ORR
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: MRD negative response rate in peripheral blood
Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: MRD-negative CR rate in peripheral blood
Up to 48 months post treatment
- +43 more secondary outcomes
Study Arms (5)
Phase 1 JCAR017 monotherapy
EXPERIMENTALSubjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)
Phase 1 JCAR017 + ibrutinib
EXPERIMENTALSubjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm + ibrutinib
Phase 2 JCAR017 monotherapy
EXPERIMENTALSubjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm
Phase 1 JCAR017 + venetoclax
EXPERIMENTALSubjects will receive venetoclax as bridging anticancer therapy until lymphodepletion chemotherapy/ JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm. After JCAR017 infusion subjects will receive venetoclax until Day 90.
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion (DEME)
EXPERIMENTALSubjects will receive JCAR017 monotherapy
Interventions
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants will receive venetoclax as bridging anticancer therapy on a weekly ramp up dosing schedule until stopping one day prior to lymphodepletion. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection, and the day after infusion venetoclax will be re-initiated.
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive bridging anticancer therapy for disease control. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.
Participants eligible for this cohort should be receiving ibrutinib at the time of screening. For participants who previously discontinued ibrutinib, ibrutinib will be started as soon as possible after eligibility is confirmed. Ibrutinib treatment will continue for up to 90 days after JCAR017 infusion (or longer for participants who are receiving benefit from ibrutinib). Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive bridging chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.
Eligibility Criteria
You may qualify if:
- Diagnosis of:
- CLL with an indication for treatment based on the Investigator's opinion and measurable disease, or
- SLL (lymphadenopathy and/or splenomegaly and \< 5×10\^9 CD19+ CD5+ clonal B lymphocytes/L \[\< 5000/µL\] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL)
- Subjects (other than those in the ibrutinib + JCAR017 combination therapy and DEME cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy.
- Subjects in the JCAR017 monotherapy cohorts must have received previous treatment as follows:
- Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy.
- Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
- DEME cohort ONLY: Subjects with relapsed or refractory CLL or SLL, irrespective of cytogenetic risk features, must have received at least 2 lines of prior therapy including a BTKi and a BCL2i.
- Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:
- be receiving ibrutinib and progressing at the time of study enrollment
- have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib
- have previously received ibrutinib and have no contraindications to restarting ibrutinib
- Eastern Cooperative Oncology Group performance status of ≤ 1
- Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy
- Adequate organ function, defined as:
- +14 more criteria
You may not qualify if:
- Subjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
- History of another primary malignancy that has not been in remission for at least 2 years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer, completely resected stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.)
- Subjects with Richter's transformation
- Prior treatment with any gene therapy product
- Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection
- Systemic fungal, bacterial, viral, or other infection that is not controlled
- Presence of acute or extensive chronic graft versus host disease (GVHD)
- 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, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,cerebral edema, or psychosis
- Pregnant or nursing (lactating) women
- Use of any of the following medications or treatments within the noted time prior to leukapheresis:
- Alemtuzumab within 6 months prior to leukapheresis
- Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis
- Cladribine within 3 months prior to leukapheresis
- Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (86)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
University of Alabama Birmingham
Birmingham, Alabama, 35294, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
City of Hope
Duarte, California, 91010, United States
City Of Hope
Duarte, California, 91010, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University Of California San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Local Institution - 0059
Los Angeles, California, 90095, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
Local Institution - 0010
San Francisco, California, 94143, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
Local Institution - 0110
Newark, Delaware, 19713, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Local Institution - 0085
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
Local Institution - 0104
Atlanta, Georgia, 30322, United States
Local Institution - 0019
Atlanta, Georgia, 30342, United States
The Blood and Marrow Transplant Group of Georgia (BMTGA)
Atlanta, Georgia, 30342, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
University Of Chicago Medical Center
Chicago, Illinois, 60637, United States
Franciscan St. Francis Health - Indiana Blood and Marrow Transplantation (IBMT)
Indianapolis, Indiana, 46237, United States
Local Institution - 0107
Wichita, Kansas, 67124, United States
Norton Healthcare - Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Local Institution - 0027
New Orleans, Louisiana, 70112, United States
Local Institution - 0005
Boston, Massachusetts, 02114, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Local Institution - 0015
Boston, Massachusetts, 02215, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-5362, United States
University Of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Local Institution - 0062
Detroit, Michigan, 48201, United States
Local Institution - 0109
Detroit, Michigan, 48202, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
University Of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Memorial Sloan-Kettering Cancer Center (MSKCC) - Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Astera Cancer Care
Edison, New Jersey, 08820, United States
John Theurer Cancer Center
Hackensack, New Jersey, 07601-2191, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Atlantic Health System / Morristown Medical Center
Morristown, New Jersey, 07960, United States
Local Institution - 0077
New Brunswick, New Jersey, 08903, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Local Institution - 0035
New York, New York, 10021, United States
Columbia University Medical Center
New York, New York, 10032, United States
Local Institution - 0026
New York, New York, 10032, United States
Weill Cornell Medical College
New York, New York, 10065, United States
Stony Brook University
Stony Brook, New York, 11794-8160, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
University Hospitals Seidman Cancer Center (Case Western)
Cleveland, Ohio, 44106-5061, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center (Stephenson Cancer Center)
Oklahoma City, Oklahoma, 73104, United States
University of Oklahoma Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Local Institution - 0098
Eugene, Oregon, 97401, United States
University of Pennsylvania - Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104, United States
University of Pennsylvania Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University - Clinical Research Institute
Philadelphia, Pennsylvania, 19107, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Local Institution - 0029
Pittsburgh, Pennsylvania, 15232, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Sarah Cannon Research Institute - Tennessee Oncology
Nashville, Tennessee, 37203, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
Local Institution - 0083
Dallas, Texas, 75390, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Local Institution - 0079
Dallas, Texas, 75426, United States
The University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Local Institution - 0028
Salt Lake City, Utah, 84112, United States
Local Institution - 0113
Charlottesville, Virginia, 22903, United States
Local Institution - 0087
Richmond, Virginia, 23298, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Seattle Cancer Center Alliance
Seattle, Washington, 98109, United States
Froedtert Hospital BMT Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Local Institution - 0112
Toronto, Ontario, M5G 2C1, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1, Canada
Related Publications (3)
Siddiqi T, Maloney DG, Kenderian SS, Brander DM, Dorritie K, Soumerai J, Riedell PA, Shah NN, Nath R, Fakhri B, Stephens DM, Ma S, Feldman T, Solomon SR, Schuster SJ, Perna SK, Tuazon SA, Ou SS, Papp E, Peiser L, Chen Y, Wierda WG. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet. 2023 Aug 19;402(10402):641-654. doi: 10.1016/S0140-6736(23)01052-8. Epub 2023 Jun 6.
PMID: 37295445DERIVEDTeoh J, Brown LF. Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. Cytotherapy. 2022 Sep;24(9):962-973. doi: 10.1016/j.jcyt.2022.03.013. Epub 2022 May 21.
PMID: 35610089DERIVEDSiddiqi T, Soumerai JD, Dorritie KA, Stephens DM, Riedell PA, Arnason J, Kipps TJ, Gillenwater HH, Gong L, Yang L, Ogasawara K, Thorpe J, Wierda WG. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL. Blood. 2022 Mar 24;139(12):1794-1806. doi: 10.1182/blood.2021011895.
PMID: 34699592DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Central Study Contacts
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACT
First line of the email MUST contain NCT # and Site #.
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 29, 2017
First Posted
November 6, 2017
Study Start
November 27, 2017
Primary Completion (Estimated)
November 26, 2027
Study Completion (Estimated)
November 26, 2027
Last Updated
March 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- See Plan Description
- Access Criteria
- See Plan Description
BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html