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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Small Lymphocytic
• Intervention / Treatment: Biological: JCAR017 (lisocabtagene maraleucel) + ibrutinib; Biological: JCAR017 (lisocabtagene maraleucel) + venetoclax; Biological: JCAR017 (lisocabtagene maraleucel)

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35294
      • Local Institution - 0006
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Gilbert, Arizona, United States, 85234
      • Local Institution - 0043
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Duarte, California, United States, 91010-301
      • Local Institution - 0007
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • La Jolla, California, United States, 92093
      • Local Institution - 0025
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90095
      • Local Institution - 0059
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • San Francisco, California, United States, 94143
      • Local Institution - 0010
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20007
      • Local Institution - 0085
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jacksonville, Florida, United States, 32224
      • Local Institution - 0080
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 0019
    • Atlanta, Georgia, United States, 30342
      • The Blood and Marrow Transplant Group of Georgia (BMTGA)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0003
    • Chicago, Illinois, United States, 60637
      • Local Institution - 0016
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0015
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0005
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5362
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0084
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201
      • Local Institution - 0062
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0054
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68198
      • Local Institution - 0008
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601-2191
      • Local Institution - 0038
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Local Institution - 0077
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10021
      • Local Institution - 0035
    • New York, New York, United States, 10032
      • Local Institution - 0026
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27705
      • Local Institution - 0030
  • Ohio
    • Cleveland, Ohio, United States, 44106-5061
      • University Hospitals Seidman Cancer Center (Case Western)
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 0078
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center (Stephenson Cancer Center)
    • Oklahoma City, Oklahoma, United States, 73104
      • Local Institution - 0082
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Local Institution - 0098
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Perelman Center for Advanced Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0088
    • Philadelphia, Pennsylvania, United States, 19107
      • Local Institution - 0032
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0029
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75426
      • Local Institution - 0079
    • Dallas, Texas, United States, 75390
      • Local Institution - 0083
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Local Institution - 0002
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
    • Salt Lake City, Utah, United States, 84112
      • Local Institution - 0028
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Local Institution - 0087
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Local Institution - 0018
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Local Institution - 0055

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of:

  1. CLL with an indication for treatment based on the Investigator's opinion and measurable disease, or
  2. 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 cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy.

• Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must have received previous treatment as follows:

  1. Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy.
  2. Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.

• Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:

  1. be receiving ibrutinib and progressing at the time of study enrollment
  2. be receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a
  3. have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib
  4. 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:

  1. Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance > 30 mL/min
  2. Alanine aminotransferase ≤ 5 × ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic infiltration of the liver)
  3. Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air
  4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% as assessed by echocardiogram or multiple uptake gated acquisition scan performed within 30 days prior to determination of eligibility
• Subject either currently has central vascular access or is a candidate to receive central vascular access or peripheral vascular access for leukapheresis procedure.
• If prior CD19-targeted therapy has been administered, subject must have CD19-positive disease confirmed by immunohistochemistry or flow cytometry since completing the prior CD19-targeted therapy.
• Subjects in ibrutinib + JCAR017 combination cohort must have progressed on a BTKi and have received prior therapy with venetoclax

• Subjects in venetoclax + JCAR017 combination cohort must:

  1. have failed at least 1 prior line of therapy, including failed BTKi therapy or have been deemed ineligible to receive BTKi
  2. be venetoclax naive (required for dose expansion) or
  3. if prior venetoclax (only for dose escalation)
  4. have no contraindictions to re-initiation of venetoclax based on prior intolerance and have had at least 6 months elapsed since the last dose of venetoclax, if either, best response was stable disease, or subject experienced disease progression on venetoclax, or within 6 months of venetoclax discontinuation
• subjects in the venetoclax + JCAR017 combination must have hemoglobin >=9 g/dL, absolute neutrophil count >=500mm3 and platelets>= 75,000/mm3, unless cytopenias are judged by investigator to be due to CLL infiltration of the bone marrow
• must have diagnosis of CLL or SLL with an indication for treatment based on the investigator's opinion and measurable disease (any of the following measurable lymph nodes ≥1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly) and demonstration of CLL cells in the peripheral blood by flow cytometry

Exclusion Criteria:

• 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:

  1. Alemtuzumab within 6 months prior to leukapheresis
  2. Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis
  3. Cladribine within 3 months prior to leukapheresis
  4. Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis
  5. Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis
  6. Fludarabine within 4 weeks prior to leukapheresis
  7. GVHD therapies such as calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive antibodies (such as anti-tumor necrosis factor-α [TNFα], anti-interleukin-6 [IL-6], or anti-interleukin-6 receptor [IL 6R]) within 4 weeks prior to leukapheresis
  8. Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
  9. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis
  10. Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis
  11. Venetoclax within 4 days prior to leukapheresis
  12. Idelalisib or duvelisib within 2 days prior to leukapheresis
  13. Lenalidomide within 1 day prior to leukapheresis
  14. Experimental agents, including off-label use of approved drugs (with the exception of acalabrutinib which may be continued up to the day before leukapheresis), within 4 weeks prior to leukapheresis unless progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or subject unwillingness or inability to follow the procedures required in the protocol
• Progressive vascular tumor invasion, thrombosis, or embolism
• Deep vein thrombosis or embolism not managed on a stable regimen of anticoagulation
• Use of any of the following medications or treatments within the noted time prior to leukapheresis lenalidomide or acalabrutinib within 1 day prior to leukapheresis experimental agents, including off-label use of approved drugs, within 4 weeks prior to leukapheresis.
• Venous thrombosis or embolism requiring treatment but not managed on a stable regimen of anticoagulation
• For subjects in the venetoclax + JCAR017 combination cohorts only, concomitant treatment with CYP3A moderate/strong inducers or moderate/strong inhibitors which cannot be discontinued

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 JCAR017 monotherapy; Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)	Biological: JCAR017 (lisocabtagene maraleucel); 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.
Experimental: Phase 1 JCAR017 + ibrutinib; Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm + ibrutinib	Biological: JCAR017 (lisocabtagene maraleucel) + ibrutinib; 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.
Experimental: Phase 2 JCAR017 monotherapy; Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm	Biological: JCAR017 (lisocabtagene maraleucel); 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.
Experimental: Phase 1 JCAR017 + venetoclax; Subjects 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.	Biological: JCAR017 (lisocabtagene maraleucel) + venetoclax; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 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 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 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: ORR	Defined as the rate of CR (including CRi)	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: adverse events	Proportion of subjects experiencing adverse events	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion 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: MRD negative response rate in peripheral blood	Proportion of subjects who achieve MRD CR	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: MRD-negative CR rate in peripheral blood	Proportion of subjects who achieve MRD CR	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Duration of response (DOR)	Defined as the time from first response (CR, CRi, nPR, or PR) to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Duration of complete response (DoCR)	Defined as the time from first CR or CRi to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Time to response (TTR)	Defined as the interval from JCAR017 infusion to the first documentation of CR, CRi, nPR, or PR	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: PFS	Defined as the time from JCAR017 infusion to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: OS	Defined as the time from JCAR017 infusion to the date of death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Time to complete response (TTCR)	Defined as the interval from JCAR017 infusion to the first documentation of CR	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: ORR	Defined as the rate of CR (including CRi)	Through post treatment Day 90
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: adverse events	Proportion of subject experiencing adverse events	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: lab abnormalities	Proportion of subjects experiencing laboratory abnormalities	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: MRD-negative response rate in peripheral blood	Proportion of subjects who achieve MRD CR	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: MRD-negative CR rate in peripheral blood	Proportion of subjects who achieve MRD CR	Through post treatment Day 90
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Duration of response (DOR)	Defined as the time from first response (CR, CRi, nPR, or PR) to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Duration of complete response (DoCR)	Defined as the time from first CR or CRi to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Time to response (TTR)	Defined as the interval from JCAR017 infusion to the first documentation of CR, CRi, nPR, or PR	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Time to complete response (TTCR)	Defined as the interval from JCAR017 infusion to the first documentation of CR	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: PFS	Defined as the time from JCAR017 infusion to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: OS	Defined as the time from JCAR017 infusion to the date of death due to any cause	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: adverse events	Proportion of subjects experiencing adverse events	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: laboratory abnormalities	Proportion of subjects experiencing laboratory abnormalities	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: ORR	Defined as the rate of CR (including CRi)	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: MRD negative response rate in peripheral blood	Proportion of subjects who achieve MRD CR	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: MRD-negative CR rate in peripheral blood	Proportion of subjects who achieve MRD CR	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: Duration of response (DOR)	Defined as the time from first response (CR, CRi, nPR, or PR) to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: Duration of complete response (DoCR)	Defined as the time from first CR or CRi to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: Time to response (TTR)	Defined as the interval from JCAR017 infusion to the first documentation of CR, CRi, nPR, or PR	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: Time to complete response (TTCR)	Defined as the interval from JCAR017 infusion to the first documentation of CR	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: PFS	Defined as the time from JCAR017 infusion to the earlier date of PD or death due to any cause	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: OS	Defined as the time from JCAR017 infusion to the date of death due to any cause	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: Health-related quality of life (HRQoL) questionnaire	Change from baseline in HRQoL assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: HRQoL questionnaire	Change from baseline in HRQoL assessed using the EORTC chronic lymphocytic leukemia (CLL)-specific module QLQ-CLL-17	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: Health economics and outcomes research (HEOR) questionnaire	Change from baseline in measurement of health utility values using EuroQol instrument EQ-5D-5L	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: HEOR questionnaire	Proportion of participants with intensive care unit (ICU) inpatient days	Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: HEOR questionnaire	Proportion of participants with non-ICU inpatient days	Up to 48 months post treatment

Collaborators and Investigators

• Sponsor: Juno Therapeutics, a Subsidiary of Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Teoh 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.
• Siddiqi 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Estimated): July 13, 2026
• Study Completion (Estimated): July 13, 2026

Study Registration Dates

• First Submitted: October 29, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: TRANSCEND_CLL_004
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: 017004; TRANSCEND-CLL-004 (Other Identifier: Juno Therapeutics, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No