Relmacabtagene Autoleucel As Second-Line Therapy in Adult Patients with Aggressive B-cell NHL: a Single-arm, Multicenter, Open, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 46
- 试验地点
- 13
- 主要终点
- ORR at 3 month
研究概览
简要总结
The primary objective of this study is to asess the efficacy of Relmacabtagene autoleucel as second-line therapy in adult patients with aggressive B-cell Non-Hodgkins Lymphoma who are ineligible for haematopoietic stem cell transplantation.
详细描述
This is an open-label, multicenter, Phase 2 study to determine the antitumor activity, PK, and safety of JWCAR029(Relmacabtagene autoleucel ) in subjects who have relapsed within 12 months from, or are refractory to, a single line of immunochemotherapy for aggressive Bcell NHL and are ineligible for HSCT (as defined in the eligibility criteria). Subjects will be treated with lymphodepleting chemotherapy and JWCAR029.
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
- •Age≥18 years;
- •Signed written informed consent obtained prior to any study procedures;
- •Histologically confirmed relapsed or refractory (R/R) aggressive B-cell NHL of the following histologiesLBCL as defined by the World Health Organization (WHO) Classification 2022:Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), high-grade B-cell lymphoma (HGL) with MYC and BCL2 rearrangements,HGL-NOS, Primary mediastinal large B-cell lymphoma, Follicular lymphoma Grade 3B (FL3B),Indolent B-NHL-transformed large B-cell lymphoma with adequate prior treatment with anthracycline-containing agents and rituximab or other CD20-targeted agents;
- •Subjects must meet the definition of refractory or relapsed;
- •Subjects were not eligible for HDCT/ASCT based on the investigator's assessment ;
- •Adequate organ function;
- •Presence of positive PET assessable lesions as determined by the Lugano criteria ;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- •Expected survival greater than 12 weeks;
- •Adequate vascular access for leukapheresis procedure;
- •Women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 2 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 2 year after Relmacabtagene Autoleucel infusion;
排除标准
- •Subjects with non-Hodgkin's lymphoma who have received second or more line therapy;
- •Lymphoma of the primary center (subjects with secondary central nervous system lymphoma are allowed to enroll;
- •History of another primary malignancy that has not been in remission for at least 2 years;
- •Subjects has active 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;
- •Uncontrolled diabetes and hypertension;
- •Presence of acute or chronic graft-versus-host disease (GVHD);
- •Active autoimmune disease requiring immunosuppressive therapy;
- •History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
- •Pregnant or nursing women;
- •Subjects Received an autologous or allogeneic hematopoietic stem cell transplant;
- •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;
- •Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy;
- •History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.
研究组 & 干预措施
Relmacabtagene Autoleucel
Experimental: Relmacabtagene Autoleucel Participants will receive cyclophosphamide250 mg/m^2/day intravenously (IV) and fludarabine 25 mg/m^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day1.
干预措施: Relmacabtagene Autoleucel (Biological)
Relmacabtagene Autoleucel
Experimental: Relmacabtagene Autoleucel Participants will receive cyclophosphamide250 mg/m^2/day intravenously (IV) and fludarabine 25 mg/m^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day1.
干预措施: Fludarabine (Drug)
Relmacabtagene Autoleucel
Experimental: Relmacabtagene Autoleucel Participants will receive cyclophosphamide250 mg/m^2/day intravenously (IV) and fludarabine 25 mg/m^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day1.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
ORR at 3 month
时间窗: 3 months
Percentage of participants with CR \[CMR;CRR\] or PR \[partial metabolic response (PMR);
次要结局
- Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel(up to 1 year after Relmacabtagene Autoleucel infusion)
- Duration of partial remission (DoPR)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Overall Survival (OS)(up to 2 year after Relmacabtagene Autoleucel infusion)
- Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel(up to 1 year after Relmacabtagene Autoleucel infusion)
- Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel(up to 1 year after Relmacabtagene Autoleucel infusion)
- The concentration of Car-T cell(up to 1 year after Relmacabtagene Autoleucel infusion)
- Duration of complete remission (DoCR)(up to 2 years after Relmacabtagene Autoleucel infusion)
- CRR at 3 month(3 months)
- Duration of response (DOR)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Time to response (TTR)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Progression-Free Survival (PFS)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Adverse events (AEs)(up to 2 year after Relmacabtagene Autoleucel infusion)