临床试验/NCT03331198

NCT03331198进行中（未招募）1 期

An Open-Label, Phase 1/2 Study of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)

Juno Therapeutics, a Subsidiary of Celgene144 个研究点分布在 1 个国家目标入组 320 人开始时间: 2017年11月27日最近更新: 2026年7月6日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 320
试验地点: 144
主要终点: Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: adverse events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

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.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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
•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
•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.
•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:
•have failed at least 1 prior line of therapy, including failed BTKi therapy or have been deemed ineligible to receive BTKi
•be venetoclax naive (required for dose expansion) or
•if prior venetoclax (only for dose escalation)
•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

排除标准

•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
•Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis
•Fludarabine within 4 weeks prior to leukapheresis
•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
•Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
•Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis
•Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis
•Venetoclax within 4 days prior to leukapheresis
•Idelalisib or duvelisib within 2 days prior to leukapheresis
•Lenalidomide or covalent and non-covalent BTKi within 1 day prior to leukapheresis
•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

研究组 & 干预措施

Phase 1 JCAR017 + ibrutinib

Experimental

Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm + ibrutinib

干预措施: JCAR017 (lisocabtagene maraleucel) + ibrutinib (Biological)

Phase 2 JCAR017 monotherapy

Experimental

Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm

干预措施: JCAR017 (lisocabtagene maraleucel) (Biological)

Phase 1 JCAR017 + venetoclax

Experimental

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.

干预措施: JCAR017 (lisocabtagene maraleucel) + venetoclax (Biological)

Phase 2 JCAR017 Double-Exposed Monotherapy Expansion (DEME)

Experimental

Subjects will receive JCAR017 monotherapy

干预措施: JCAR017 (lisocabtagene maraleucel) (Biological)

Phase 1 JCAR017 monotherapy

Experimental

Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)

干预措施: JCAR017 (lisocabtagene maraleucel) (Biological)

结局指标

主要结局

Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: adverse events

时间窗: Up to 48 months post treatment

Proportion of subjects experiencing adverse events

Phase 1 JCAR017 and ibrutinib combination dose escalation therapy arm: laboratory abnormalities

时间窗: Up to 48 months post treatment

Proportion of subjects experiencing laboratory abnormalities

Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm

时间窗: Through post treatment up to Month 48

Proportion of subjects who have CR after treatment with JCAR017 + ibrutinib using iwCLL 2018 guidelines

Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: adverse events

时间窗: Up to 48 months post treatment

Proportion of subjects experiencing adverse events

Phase 2 JCAR017 monotherapy expansion arm

时间窗: Through post treatment up to Month 48

Proportion of subjects who have CR after treatment with JCAR017 using iwCLL 2018 guidelines

Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: laboratory abnormalities

时间窗: Up to 48 months post treatment

Proportion of subjects experiencing laboratory abnormalities

Phase 1 JCAR017 monotherapy arm: adverse events

时间窗: Up to 48 months post treatment

Proportion of subjects experiencing adverse events

Phase 2 JCAR017 Double exposed monotherapy expansion arm: overall response rate (ORR)

时间窗: Up to approximately 24 months

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

Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm

时间窗: Through post treatment up to Month 48

Proportion of subjects who have CR after treatment with JCAR017 + venetoclax using iwCLL 2018 guidelines

Phase 1 JCAR017 monotherapy arm: laboratory abnormalities

时间窗: Up to 48 months post treatment

Proportion of subjects experiencing laboratory abnormalities

次要结局

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)
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Duration of complete response (DoCR)(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: adverse events(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: MRD-negative response rate in peripheral blood(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Duration of complete response (DoCR)(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: lab abnormalities(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: ORR(Through post treatment Day 90)
Phase 2 JCAR017 Monotherapy Expansion Arm: laboratory abnormalities(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: ORR(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: MRD-negative CR rate in peripheral blood(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: adverse events(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: Time to response (TTR)(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: Time to complete response (TTCR)(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: OS(Up to 48 months post treatment)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: adverse events(Up to approximately 24 months)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: MRD-negative response rate in peripheral blood(Up to approximately 24 months)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Time to complete response (TTCR)(Up to approximately 24 months)
Phase 2 JCAR017 Monotherapy Expansion Arm: Duration of response (DOR)(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: Duration of complete response (DoCR)(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: PFS(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: Health-related quality of life (HRQoL) questionnaire(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: Health economics and outcomes research (HEOR) questionnaire(Up to 48 months post treatment)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Time to response (TTR)(Up to approximately 24 months)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Progression free survival (PFS)(Up to approximately 24 months)
Phase 2 JCAR017 Monotherapy Expansion Arm: HRQoL questionnaire(Up to 48 months post treatment)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: MRD-negative CR rate in peripheral blood(Up to approximately 24 months)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: laboratory abnormalities(Up to approximately 24 months)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Duration of response (DOR)(Up to approximately 24 months)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: CR rate(Up to approximately 24 months)
Phase 2 JCAR017 Monotherapy Expansion Arm: HEOR questionnaire(Up to 48 months post treatment)
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: Time to complete response (TTCR)(Up to 48 months post treatment)
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Duration of response (DOR)(Up to 48 months post treatment)
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: Time to response (TTR)(Up to 48 months post treatment)
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: PFS(Up to 48 months post treatment)
Phase 1 JCAR017 and ibrutinib combination dose expansion therapy arm: OS(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Time to response (TTR)(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Time to complete response (TTCR)(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: PFS(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: OS(Up to 48 months post treatment)
Phase 2 JCAR017 Monotherapy Expansion Arm: MRD negative response rate in peripheral blood(Up to 48 months post treatment)
Phase 1 JCAR017 and venetoclax combination dose escalation therapy arm: MRD-negative CR rate in peripheral blood(Through post treatment Day 90)
Phase 1 JCAR017 and venetoclax combination dose expansion therapy arm: Duration of response (DOR)(Up to 48 months post treatment)
Phase 2 JCAR017 Double-Exposed Monotherapy Expansion Arm: Overall Survival (OS)(Up to approximately 24 months)

研究者

发起方

Juno Therapeutics, a Subsidiary of Celgene

申办方类型

Industry

责任方

Sponsor

研究点 (144)

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