Study to Evaluate the Efficacy and Safety of Relmacabtagene Autoleucel (Relma-cel) as First-Line Therapy in Adult Participants With High-Risk Large B-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
研究概览
简要总结
The primary objective of this study is to estimate the efficacy of Relmacabtagene Autoleucel in participants with high-risk large B-cell lymphoma.
详细描述
This is a prospective, open-label, multicenter, single-arm trial, assessed the efficacy and safety of JWCAR029(relma-cel) as part of first-line therapy after an incomplete first-line treatment regimen of two cycles of chemoimmunotherapy. High-risk LBCL was defined by the dynamic risk assessment of interim PET2+, together with either double- or triple-hit lymphomas or high-intermediate- and high-risk IPI scores (≥3). 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
- •≥ 18 years old;
- •Sign on the informed consent;
- •Histologically confirmed large B-cell lymphoma that also meets the definition of high-risk large B-cell lymphoma as a lymphoma International Prognostic Index (IPI) score of 3-5 and/or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (double/triple-hit lymphoma) (DHL/THL) and must be treated with 2 cycles of CD20 monoclonal antibodies combined with anthracyclines. Presence of positive PET assessable lesions (DS score of 4 or 5) as determined by the Lugano criteria (Cheson et al., 2014)；
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Expected survival greater than 12 weeks；
- •Adequate organ function：
- •Absolute neutrophil count ≥ 1000/μL；Absolute lymphocyte count ≥ 100/μL； Platelet count ≥ 75,000/μL；Hb ≥ 80g/L；
- •Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (Cockcroft-Gault formula) > 50 mL/min (serum creatinine clearance due to lymphoma mass compression should be > 30 mL/min)；
- •Serum alanine aminotransferase (ALT) ≤ 5 upper limit of normal (ULN) and total bilirubin ≤2ULN（or for subjects with Gilbert's syndrome or lymphoma invading the liver < 3 ULN）；
- •Baseline oxygen saturation > 92% on room air；
- •Left ventricular ejection fraction (LVEF) ≥50% assessed by echocardiography or radionuclide activity angiography (MUGA) within 1 month of enrollment；
- •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 1 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after Relmacabtagene Autoleucel infusion.
排除标准
- •Lymphoma involving the central nervous system (CNS)；
- •History of another primary malignancy that has not been in remission for at least 2 years;
- •History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma；
- •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 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
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 Day 1.
干预措施: Relmacabtagene Autoleucel (Biological)
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 Day 1.
干预措施: Fludarabine (Drug)
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 Day 1.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
时间窗: up to 2 years after Relmacabtagene Autoleucel infusion
Complete Response Rate (CRR): percentage of participants with CR \[complete metabolic response (CMR); complete radiological response (CRR)\]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.
次要结局
- Overall Survival (OS)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators(up to 2 years after Relmacabtagene Autoleucel infusion)
- Duration of Response (DOR) Per the Lugano Classification(up to 2 years after Relmacabtagene Autoleucel infusion)
- Event-Free Survival (EFS)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Progression-Free Survival (PFS)(up to 2 years after Relmacabtagene Autoleucel infusion)
- Types, frequency, and severity of adverse events and laboratory anomalies(up to 2 years after Relmacabtagene Autoleucel infusion)
- Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel(up to 1 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)
- The change of serum cytokines concentration(up to 1 year after Relmacabtagene Autoleucel infusion)