A Single-Arm Clinical Study of CD19 CAR-T Following ASCT for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) With High-Risk Prognostic Factors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Best Complete Response (CR) Rate in 3 months
研究概览
简要总结
Clinical trial for the safety and efficacy of CD19 CAR-T following autologous hematopoietic stem cell transplantation (ASCT) for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) with High-Risk Prognostic Factors
详细描述
This is a single-center, single-arm, open-label, prospective clinical trial to evaluate the efficacy and safety of CD19 CAR-T infusion following high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT) in relapsed or refractory B-cell Non-Hodgkin's Lymphoma patients with high-risk prognostic factors (extranodal involvement/bulky mass ≥5 cm in diameter/TP53 alterations). CD19 CAR-T will be infused on day +3 (±1d) with a fixed dose of 100X10^6. The study will assess the safety and efficacy of this combinational therapy, including the investigators assessed the best complete response rate (BCR) in 3 months (primary endpoint), objective response rates, survivals, incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematological, and other non-hematological toxicities of the subjects.
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
- •Histologically confirmed B-cell non-Hodgkin's lymphoma including the following types
- •diffuse large B-cell lymphoma
- •high-grade B-cell lymphoma with or without MYC and BLC2 and/or BCL6 rearrangement
- •transformed lymphoma
- •primary mediastinal large B-cell lymphoma
- •follicular lymphoma (FL)
- •Relapsed or refractory diseases fulfilling one of the following criteria (individuals must have received anti-CD20 monoclonal antibody and anthracycline-containing chemotherapy regimen)
- •Primary refractory disease, defined as disease progression after first-line immunochemotherapy or disease progression within 6 weeks of the end of the last chemotherapy
- •Stable disease (SD) as best response after at least 4 cycles of first-line therapy
- •Partial response (PR) as best response after at least 6 cycles of first-line therapy (biopsy-proven residual disease is needed for individuals with Deauville score of 4)
- •PR as best response after at least 2 cycles of second-line therapy
- •Disease relapse ≤12 months after the completion of first-line immunochemotherapy
- •Relapsed or refractory disease after ≥2 lines of chemotherapy
- •Presence of at least one of the following high-risk prognostic factors: (1) extranodal involvement; (2) maximum diameter of the bulky mass ≥5 cm; (3) TP53 gene alterations
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Eligible for HDCT/ASCT based on the investigator's assessment and are scheduled to undergo an ASCT sequential CAR-T treatment regimen
- •Adequate renal and hepatic function defined as:
- •Serum alanine aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN)
- •Total bilirubin ≤1.5 mg/dL(<3 times ULN in patients with Gilbert's syndrome, cholestasis due to hepatoportal compression adenopathy, biliary obstruction in patients with liver involvement or lymphoma)
- •Serum creatinine ≤1.5 ULN, or creatinine clearance (as estimated by Cockcroft Gault) ≥ 30 mL/min
- •Cardiac ejection fraction ≥ 40%
- •Baseline oxygen saturation > 95% on room air
- •Life expectancy ≥3 months
排除标准
- •History of autologous or allogeneic stem cell transplantation
- •Active HBV or HCV infection, defined as HBV-DNA or HCV-DNA levels above the normal upper limit, with or without abnormal liver function. Individuals with positive HBsAg or HBcAb should receive antiviral prophylaxis for at least 12 months after CAR-T cells infusion.
- •Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease.
- •History of HIV infection
- •Prior chimeric antigen receptor cellular immunotherapy targeting CD19
- •Pregnant or lactating patients
研究组 & 干预措施
CAR-T following ASCT
Participants will receive high-dose chemotherapy followed by stem-cell infusion, and a fixed dose of CAR-T cells will be infused.
干预措施: Relmacabtagene autoleucel (relma-cel) (Drug)
CAR-T following ASCT
Participants will receive high-dose chemotherapy followed by stem-cell infusion, and a fixed dose of CAR-T cells will be infused.
干预措施: autologous stem-cell transplantation (Other)
结局指标
主要结局
Best Complete Response (CR) Rate in 3 months
时间窗: 3months post CAR-T infusion
Best Complete Response rate in 3 months is defined as the incidence of subjects achieving complete remission (CR) within 3 months after CAR-T infusion according to the Lugano Classification (Cheson et al, 2014), as determined by study investigators.
次要结局
- Objective remission rate (ORR) in 3months(3months post CAR-T infusion)
- Duration of Response (DOR)(2 years post CAR-T infusion)
- Overall Survival (OS)(2 years post CAR-T infusion)
- Progression-Free Survival (PFS)(2 years post CAR-T infusion)
- Adverse Events rate as assessed by CTCAE version 5.0(2 years post CAR-T infusion)