October 29, 2017
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November 6, 2017
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August 28, 2020
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December 26, 2017
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October 12, 2021 (Final data collection date for primary outcome measure)
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- Phase 1 monotherapy arm: recommended dose [ Time Frame: 28 days ]
Recommended dose based on assessment of data from each dose level
- Phase 1 combination therapy arm: adverse events [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects experiencing adverse events
- Phase 1 combination therapy arm: laboratory abnormalities [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects experiencing laboratory abnormalities
- Phase 2: rate of complete remission (CR) [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects who have CR after JCAR017 infusion based on Independent Review Committee (IRC) assessment using International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines
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- Phase 1 monotherapy arm: recommended dose [ Time Frame: 28 days ]
Recommended dose based on assessment of data from each dose level
- Phase 1 combination therapy arm: adverse events [ Time Frame: 30 days ]
Proportion of subjects experiencing adverse events
- Phase 1 combination therapy arm: laboratory abnormalities [ Time Frame: 30 days ]
Proportion of subjects experiencing laboratory abnormalities
- Phase 2: antitumor activity [ Time Frame: Through post-randomization Month 24 ]
Complete response rate based on Independent Review Committee assessment using iwCLL 2008 guidelines
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- Phase 2: overall response rate [ Time Frame: Through post-treatment Month 24 ]
Overall response rate based on IRC assessment using iwCLL 2018 guidelines
- Phase 2: minimal residual disease (MRD)-negative response rate [ Time Frame: Through post-treatment Month 24 ]
MRD will be measured via IgHV deep sequencing and flow cytometry of peripheral blood
- Phase 2: adverse events [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects experiencing adverse events
- Phase 2: laboratory abnormalities [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects experiencing laboratory abnormalities
- Phase 2: overall survival [ Time Frame: Through post-treatment Month 24 ]
Overall survival
- Phase 2: progression-free survival (PFS) [ Time Frame: Through post-treatment Month 24 ]
PFS, defined as the time from JCAR017 infusion to disease progression or death
- Phase 2: health economics and outcomes research [ Time Frame: Through post-treatment Month 24 ]
EuroQol instrument EQ-5D-5L and numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
- Phase 2: health-related quality of life [ Time Frame: Through post-treatment Month 24 ]
EORTC QLQ-C30
- Phase 2: health-related quality of life [ Time Frame: Through post-treatment Month 24 ]
CLL-specific module QLQ-CLL-17
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- Phase 2: adverse events [ Time Frame: 30 days ]
Proportion of subjects experiencing adverse events
- Phase 2: laboratory abnormalities [ Time Frame: 30 days ]
Proportion of subjects experiencing laboratory abnormalities
- Phase 2: overall response rate [ Time Frame: Through post-randomization Month 24 ]
Overall response rate based on Independent Review Committee assessment using iwCLL 2008 guidelines
- Phase 2: minimal residual disease (MRD)-negative response rate [ Time Frame: Through post-randomization Month 24 ]
MRD will be measured via IgHV deep sequencing and flow cytometry of peripheral blood and bone marrow
- Phase 2: overall survival [ Time Frame: Through post-randomization Month 24 ]
Overall survival
- Phase 2: Progression-free survival [ Time Frame: Through post-randomization Month 24 ]
Progression-free survival
- Phase 2: PK [ Time Frame: Through post-randomization Month 24 ]
AUC of JCAR017 in blood and bone marrow
- Phase 2: PK [ Time Frame: Through post-randomization Month 24 ]
Cmax of JCAR017 in blood and bone marrow
- Phase 2: PK [ Time Frame: Through post-randomization Month 24 ]
Tmax of JCAR017 in blood and bone marrow
- Phase 2: health-related quality of life and health economics and outcomes research [ Time Frame: Through post-randomization Month 24 ]
EuroQol instrument EQ-5D-5L Numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
- Phase 2: health-related quality of life and health economics and outcomes research [ Time Frame: Through post-randomization Month 24 ]
EORTC QLQ-C30 Numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
- Phase 2: health-related quality of life and health economics and outcomes research [ Time Frame: Through post-randomization Month 24 ]
CLL-specific module QLQ-CLL Numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
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Not Provided
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Not Provided
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Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
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An Open-Label, Phase 1/2 Study of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)
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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. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.
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Not Provided
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Interventional
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Phase 1 Phase 2
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Allocation: Non-Randomized Intervention Model: Parallel Assignment Intervention Model Description: Phase 1: subjects will be assigned to receive JCAR017, or JCAR017 + ibrutinib Phase 2: subjects will be assigned to receive JCAR017 at the recommended dose Masking: None (Open Label) Primary Purpose: Treatment
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- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphoma, Small Lymphocytic
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- 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 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.
- 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.
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- Experimental: Phase 1 JCAR017 monotherapy
Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)
Intervention: Biological: JCAR017 (lisocabtagene maraleucel)
- Experimental: Phase 1 JCAR017 + ibrutinib
Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose + ibrutinib
Intervention: Biological: JCAR017 (lisocabtagene maraleucel) + ibrutinib
- Experimental: Phase 2 JCAR017 monotherapy
Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm
Intervention: Biological: JCAR017 (lisocabtagene maraleucel)
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Not Provided
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Recruiting
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200
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205
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July 14, 2022
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October 12, 2021 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
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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 cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy.
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Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must have received previous treatment as follows:
- Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy.
- Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
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Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:
- be receiving ibrutinib and progressing at the time of study enrollment
- 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
- 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
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Adequate organ function, defined as:
- Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance > 30 mL/min
- 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)
- Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air
- 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.
Exclusion Criteria:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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United States
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NCT03331198
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017004 TRANSCEND-CLL-004 ( Other Identifier: Juno Therapeutics, Inc. )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Undecided |
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Juno Therapeutics, a Subsidiary of Celgene
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Juno Therapeutics, a Subsidiary of Celgene
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Not Provided
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Study Director: |
Heidi Gillenwater, MD |
Juno Therapeutics, Inc. |
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Juno Therapeutics, a Subsidiary of Celgene
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August 2020
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