A Single-arm, Single-center, Open-label Clinical Study on the Efficacy and Safety of CAR-T Combined With ASCT in the Treatment of Relapsed/Refractory Large B-cell Lymphoma With High-risk Factors.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- 1-year PFS rate
研究概览
简要总结
This is a prospective, single-arm, single-center, open-label clinical study, aiming to evaluate the efficacy and safety of CAR-T combined with ASCT in the treatment of relapsed/refractory large B-cell lymphoma with high-risk factors.
详细描述
R/R LBCL with high-risk factors sequentially undergo leukapheresis, stem cell collection, bridging therapy (if applicable, at the investigator's discretion, with only one course of bridging therapy allowed), preconditioning chemotherapy phase (for CNSL patients: TB regimen, carmustine 300 mg/m² on Day -6, thiotepa 10 mg/kg on Day -5 to Day -4; for non-CNSL patients: BEAM regimen, carmustine 300 mg/m² on Day -7, etoposide 150 mg/m² on Day -6 to Day -3, cytarabine 200 mg/m² on Day -6 to Day -3, melphalan 140 mg/m² on Day -2; for patients with prior autologous hematopoietic stem cell transplantation, the investigator may develop other preconditioning regimens based on factors such as the patient's drug sensitivity and tolerability), stem cell infusion (Day 0), and CAR-T cell infusion (Day 4 to Day 7).
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
- •Histopathologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), central nervous system lymphoma (CNSL), primary mediastinal large B-cell lymphoma (PMBCL), and transformed follicular lymphoma (tFL)
- •Must have received first-line treatment with a regimen containing anti-CD20 monoclonal antibody and anthracycline
- •Meet one of the following clinical high-risk factors or molecular biological high-risk factors:
- •Clinical high-risk factors: Failure to achieve partial response (PR) after 4 cycles of first-line immunochemotherapy; or relapse within 12 months after achieving complete response (CR) with first-line immunochemotherapy; or relapse after autologous hematopoietic stem cell transplantation (ASCT); or central nervous system involvement at the time of disease relapse or progression
- •Molecular biological high-risk factors: TP53 gene mutation; or high-grade B-cell lymphoma (HGBL) with MYC and Bcl-2 rearrangements, with or without Bcl-6 rearrangement
- •ECOG 0 to 2
- •Eligible for high-dose chemotherapy/autologous hematopoietic stem cell transplantation (HDCT/ASCT) per the investigator's assessment, and planned to receive a sequential regimen of ASCT followed by CAR-T therapy
- •Hepatic and renal function meet the following criteria: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); total bilirubin ≤ 1.5 mg/dL; serum creatinine ≤ 1.5 × ULN, or creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 30 mL/min
- •Left ventricular ejection fraction (LVEF) ≥ 40%
- •Life expectancy ≥ 3 months
排除标准
- •Patients who have previously received any CD19-targeted therapy
- •Patients with CD19 negativity confirmed by immunohistochemistry (IHC)
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as HBV DNA or HCV RNA level above the upper limit of normal (ULN), with or without liver function abnormalities
- •Presence of uncontrolled infection, cardio-cerebrovascular diseases, coagulopathy, or connective tissue diseases
- •History of human immunodeficiency virus (HIV) infection
- •Pregnant or lactating patients
研究组 & 干预措施
CAR-T+ASCT
R/R LBCL with high-risk factors sequentially undergo leukapheresis, stem cell collection, bridging therapy (if applicable, at the investigator's discretion, with only one course of bridging therapy allowed), preconditioning chemotherapy phase (for CNSL patients: TB regimen, carmustine 300 mg/m² on Day -6, thiotepa 10 mg/kg on Day -5 to Day -4; for non-CNSL patients: BEAM regimen, carmustine 300 mg/m² on Day -7, etoposide 150 mg/m² on Day -6 to Day -3, cytarabine 200 mg/m² on Day -6 to Day -3, melphalan 140 mg/m² on Day -2; for patients with prior autologous hematopoietic stem cell transplantation, the investigator may develop other preconditioning regimens based on factors such as the patient's drug sensitivity and tolerability), stem cell infusion (Day 0), and CAR-T cell infusion (Day 4 to Day 7).
干预措施: Axicabtagene Ciloleucel (Biological)
结局指标
主要结局
1-year PFS rate
时间窗: From date of CAR-T infusion until the date of first documented date of disease progression or death from any cause, assessed up to 12 months
1-year progression-free survival rate
次要结局
- bORR(The best therapeutic effect within 12 months after CAR-T infusion was the proportion of subjects achieving complete remission (CR) or partial remission (PR).)
- DOR(12 months after CAR-T infusion)
- PFS(From date of CAR-T infusion until the date of first documented date of disease progression or death from any cause, assessed up to 12 months)
- OS(From date of CAR-T infusion until the date of first documented date of death from any cause, assessed up to 12 months)
- AE and SAE(All adverse events that occurred from the time of enrollment to 12 months after the CAR-T infusion)
研究者
Yang haiyan
Chief director of Lymphoma Department
Zhejiang Cancer Hospital