A Phase II Open-Label, Single-Arm, Multicenter Study of JWCAR029, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells for Relapsed and Refractory (R/R) Non-Hodgkins Lymphoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 82
- 试验地点
- 10
- 主要终点
- Objective response rate (ORR) in LBCL subjects in cohort A;
研究概览
简要总结
This is a phase II, open-label, single-arm, multicenter study to asess the efficacy and safety of JWCAR029 in adult R/R Non-Hodgkins Lymphoma subjects in China.
详细描述
This is a phase II, open-label, single-arm, multicenter study conducted in adult subjects with R/R Non-Hodgkins Lymphoma in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect the patient reported quality of life changes and immune response after JWCAR029 treatment.
There will be two cohorts of cohort A and cohort B. Large B cell lymphoma (LBCL) patients will be enrolled in cohort A and follicular lymphoma patients will be enrolled in cohort B. Two dose levels of 1.0 x 10^8 CAR+ T cells and 1.5 x 10^8 CAR+ T cells are adopted in this study in both cohorts, subjects will be randomly assigned into the two dose levels with a 1:1 ratio. All sujects will be followed for 2 years following JWCAR029 infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Subjects must meet all of the following criteria to participate in the study:
- •≥ 18 years old;
- •Sign on the informed consent;
- •Subject must have histologically confirmed large B lymphoma or follicular lymphoma;
- •Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Adequate organ function;
- •Adequate vascular access for leukapheresis procedure;
- •Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still express CD19;
- •Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of JWCAR029;
- •Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after the last dose of JWCAR029.
排除标准
- •Central nervous system (CNS) only involvement by malignancy or primary CNS lymphoma;
- •History of another primary malignancy that has not been in remission for at least 2 years;
- •Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
- •Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
- •Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
- •Presence of acute or chronic graft-versus-host disease (GVHD);
- •History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
- •Pregnant or nursing women;
- •Subjects using of any chemotherapy, corticisteriod, experiment agents, GVHD therapies, radiation, allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
- •Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
- •Received CAR T-cell or other genetically-modified T-cell therapy previously.
研究组 & 干预措施
JWCAR029 treatment
JWCAR029 be administrated in two dose level
干预措施: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells (Biological)
结局指标
主要结局
Objective response rate (ORR) in LBCL subjects in cohort A;
时间窗: 3 months
Objective response rate (ORR) in 3 month in cohort A of large B cell lymphoma (LBCL) subjects；
Complete response rate (CRR) in FL subjects in cohort B
时间窗: 3 months
Complete response rate (CRR) in 3 month in cohort B of follicular lymphoma (FL) subjects
次要结局
- Pharmacokinetic (PK)- Cmax of JWCAR029(up to 1 year after JWCAR029 infusion)
- Overall survival(3 to 5 years after JWCAR029 infusion)
- Time to complete response (TTCR)(up to 24 months after JWCAR029 infusion)
- Pharmacokinetic (PK)- AUC of JWCAR029(up to 1 year after JWCAR029 infusion)
- Quality of Life C30 questionnaire (EORTC-QLQ-C30)(up to 2 year after JWCAR029 infusion)
- Complete response rate (CRR) in cohort A of LBCL subjects(3 months)
- Adverse events (AEs)(up to 24 months after JWCAR029 infusion)
- European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L)(up to 2 year after JWCAR029 infusion)
- ICU and non-ICU hospitalization days(up to 2 year after JWCAR029 infusion)
- Changes of T cell counts, subgroups and serum cytokines(up to 2 year after JWCAR029 infusion)
- Objective response rate (ORR) in cohort B of FL subjects(3 months)
- Duration of response (DOR)(up to 24 months after JWCAR029 infusion)
- Duration of complete remission (DoCR)(up to 24 months after JWCAR029 infusion)
- Duration of partial remission (DoPR)(up to 24 months after JWCAR029 infusion)
- Time to response (TTR)(up to 24 months after JWCAR029 infusion)
- Pharmacokinetic (PK)- Tmax of JWCAR029(up to 1 year after JWCAR029 infusion)
- Progression-free survival (PFS)(3 to 5 years after JWCAR029 infusion)
- ICU and non-ICU hospitalization reasons(up to 2 year after JWCAR029 infusion)
- Changes of inflammation biomarkers-CRP(up to 1 year after JWCAR029 infusion)
- CD19 expression in tumor biopsy samples(up to 2 year after JWCAR029 infusion)
- Anti-therapeutic JWCAR029 antibody(up to 2 year after JWCAR029 infusion)
- Changes of inflammation biomarkers-serum ferritin(up to 1 year after JWCAR029 infusion)