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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
320
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.
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.
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGUniversity of Alabama Birmingham
Birmingham, Alabama, United States
RECRUITINGBanner MD Anderson Cancer Center
Gilbert, Arizona, United States
RECRUITINGBanner MD Anderson Cancer Center
Gilbert, Arizona, United States
Phase 1 JCAR017 monotherapy arm: adverse events
Proportion of subjects experiencing adverse events
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 monotherapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: adverse events
Proportion of subjects experiencing adverse events
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: 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
Time frame: 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
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to approximately 24 months
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: adverse events
Proportion of subjects experiencing adverse events
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: ORR
Defined as the rate of CR (including CRi)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Time to response (TTR)
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City of Hope
Duarte, California, United States
RECRUITINGCity Of Hope
Duarte, California, United States
RECRUITINGUC San Diego Moores Cancer Center
La Jolla, California, United States
RECRUITINGUniversity Of California San Diego Moores Cancer Center
La Jolla, California, United States
RECRUITINGLocal Institution - 0059
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGUniversity of California, Los Angeles
Los Angeles, California, United States
RECRUITING...and 76 more locations
Defined as the interval from JCAR017 infusion to the first documentation of CR, CRi, nPR, or PR
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: adverse events
Proportion of subject experiencing adverse events
Time frame: Up to 48 months post treatment
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: lab abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: 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)
Time frame: Through post treatment Day 90
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: MRD-negative response rate in peripheral blood
Proportion of subjects who achieve MRD CR
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: adverse events
Proportion of subjects experiencing adverse events
Time frame: Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: ORR
Defined as the rate of CR (including CRi)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: HEOR questionnaire
Proportion of participants with intensive care unit (ICU) inpatient days
Time frame: Up to 48 months post treatment
Phase 2 JCAR017 Monotherapy Expansion Arm: HEOR questionnaire
Proportion of participants with non-ICU inpatient days
Time frame: Up to 48 months post treatment
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: adverse events
Proportion of subjects experiencing adverse events
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: laboratory abnormalities
Proportion of subjects experiencing laboratory abnormalities
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed 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
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: CR rate
Defined as the rate of CR (including CRi) based on IRC assessment using iwCLL 2018 guidelines
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: MRD-negative response rate in peripheral blood
Proportion of subjects who achieve MRD negative status
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: MRD-negative CR rate in peripheral blood
Proportion of subjects who achieve MRD-negative CR
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Time to response (TTR)
Defined as the interval from JCAR017 infusion to the first documentation of CR, CRi, nPR, or PR
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Time to complete response (TTCR)
Define as the interval from JCAR017 infusion to the first documentation of CR
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Progression free survival (PFS)
Defined as the time from JCAR017 infusion to the earlier date of PD or death due to any cause
Time frame: Up to approximately 24 months
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Overall Survival (OS)
Defined as the time from JCAR017 infusion to the date of death due to any cause
Time frame: Up to approximately 24 months