CNCT19 Following Autologous Stem Cell Transplantation in Patients With Relapsed or Refractory Aggressive B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percentage of participants experiencing adverse events
研究概览
简要总结
The primary objective of this study is to explore the safety and efficacy of CNCT19 (a second-generation anti-CD19 CAR T-cell using 4-1BB as co-stimulatory domain provided by Juventas, Tianjin, China) infusion following ASCT in patients with relapsed or refractory B-cell lymphoma.
详细描述
This is a single-center, non-randomized, open-label, prospective clinical trial to evaluate the safety and efficacy of CNCT19 infusion following high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT) in patients with relapsed or refractory B-cell lymphoma. CNCT19 cells will be infused on day +3 (±1d) with a fixed dose of 2×10^6/kg. The study will assess the safety and efficacy of this combinational therapy, including the incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematological, and other non-hematological toxicities, and objective response rates and complete response rates and survivals 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed large B-cell 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
- •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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow function as evidenced by:
- •Absolute neutrophil count (ANC) ≥ 1000/uL
- •Platelet count≥ 75,000/uL
- •Adequate renal and hepatic function defined as:
- •Serum alanine aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN)
- •Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome
- •Serum creatinine ≤2 ULN, or creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL/min
- •Cardiac ejection fraction ≥ 50%
- •Baseline oxygen saturation > 92% on room air
- •Life expectancy ≥3 months
排除标准
- •Active Central Nervous System (CNS) involvement by lymphoma
- •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 CNCT19 infusion.
- •Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease.
- •History of seizure or other CNS disorder
- •History of HIV infection
研究组 & 干预措施
CNCT19 following ASCT
Participants will receive high-dose chemotherapy followed by stem-cell reinfusion, and a fixed dose of CNCT19 (2×10^6/kg) will be infused in a single-dose on day +2, +3 or +4.
干预措施: CNCT19 (Biological)
CNCT19 following ASCT
Participants will receive high-dose chemotherapy followed by stem-cell reinfusion, and a fixed dose of CNCT19 (2×10^6/kg) will be infused in a single-dose on day +2, +3 or +4.
干预措施: Gemcitabine Injection (Drug)
CNCT19 following ASCT
Participants will receive high-dose chemotherapy followed by stem-cell reinfusion, and a fixed dose of CNCT19 (2×10^6/kg) will be infused in a single-dose on day +2, +3 or +4.
干预措施: busulfan (Drug)
CNCT19 following ASCT
Participants will receive high-dose chemotherapy followed by stem-cell reinfusion, and a fixed dose of CNCT19 (2×10^6/kg) will be infused in a single-dose on day +2, +3 or +4.
干预措施: Melphalan Injection (Drug)
结局指标
主要结局
Percentage of participants experiencing adverse events
时间窗: from the first day of high-dose chemotherapy until 2 years post CNCT19 infusion
次要结局
- Complete Response (CR) Rate(2 years post CNCT19 infusion)
- Objective Response Rate (ORR)(2 years post CNCT19 infusion)
- Progression-Free Survival (PFS)(2 years post CNCT19 infusion)
- Duration of Response (DOR)(2 years post CNCT19 infusion)
- Disease-Free Survival (DFS)(2 years post CNCT19 infusion)
- Overall Survival (OS)(2 years post CNCT19 infusion)