Pragmatic Clinical Trial of CD19 and CD22 CAR T-cell Sequential Therapy Versus Single CD19 CAR T-cell Bridging to Transplantation for Patients With Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 353
- 试验地点
- 2
- 主要终点
- EFS in CD19 CAR and CD22 CAR-T sequential infusion (Sequential CAR group) and CD19 CAR T-cell infusion bridging to HSCT (CAR+HSCT group)
研究概览
简要总结
This is a multi-center, open-label, non-randomized, two-arm, non-inferior trial. Patients with r/r B-ALL would be assigned to the CD19 CAR and CD22 CAR T-cell sequential infusion group (Sequential CAR, Arm-1) and the CD19 CAR T-cell infusion bridging to hematopoietic stem cell transplantation group (CAR+HSCT, Arm-2), according their own discretion. Patients would be also allowed to assigned to the CD19 CAR T-cell infusion without consolidation therapies group (Single CAR, additional placebo arm) according their own discretion. The primary objective is to prospectively evaluate and compare the efficacy of CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT in the treatment of r/r B-ALL. The primary endpoint is event-free survival of children and adolescent and young adult (AYA) with r/r B-ALL a treated with CD19 CAR and CD22 CAR T-cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT. A total number of 353 subjects will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Only patients who meet all the following criteria can be included in the group:
- •Patients who were diagnosed as primary refractory or relapsed B-ALL. (Criterion-reference: NCCN, version 2.2023); All the patients matched the diagnostic criteria of ALL according to the NCCN guideline (≥20% bone marrow lymphoblasts on hematopathology review of bone marrow aspirate and biopsy materials, which were confirmed by comprehensive flow cytometric immunophenotyping, minimal residual disease analysis and karyotyping of G-banded metaphase chromosomes). Molecular characterization could be obtained via interphase fluorescence in situ hybridization (FISH) testing, reverse transcriptase polymerase chain reaction (RT-PCR) testing, comprehensive testing by next-generation sequencing (NGS) for gene fusions and pathogenic mutations, etc. Determination of the World Health Organization ALL subtypes and cytogenetic and clinical risk groups were also allowed. B-ALL patients who did not achieve a complete remission after previous therapy (including the various treatment response scenarios shown in Table 1), who did not achieve a complete remission after at least two lines of TKI agents (including the various treatment response scenarios shown in Table 1), or who had ≥1 relapses were defined as having refractory or relapsed disease. Patients who were diagnosed as CD19- and CD22-positive high-risk B-ALL with continuous positive minimal residual disease (MRD) for more than three months after last therapy were also eligible. Patients had positive CD19 and CD22 expression on leukemia blasts by FCM (>80% CD19 and CD22 positive);
- •Age from 1 to 70 years old;
- •No serious allergic constitution;
- •Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) score 0 to 2;
- •Have life expectancy of at least 60 days based on investigator's judgement;
- •Voluntary informed consent is signed by self-aware patients aged 8-70 years and by legal representatives (guardians) of pediatric patients under 18 years of age.
排除标准
- •Patients with at least one of the following conditions are excluded:
- •Intracranial hypertension or unconscious;
- •Acute heart failure or severe arrhythmia;
- •Acute respiratory failure;
- •Other types of malignant tumors;
- •Diffuse intravascular coagulation;
- •Serum creatinine and/or blood urea nitrogen over 1.5 times the normal value;
- •Sepsis or other uncontrolled infection;
- •Uncontrolled diabetes mellitus;
- •Severe psychological disorder;
- •Obvious cranial lesions by cranial MRI;
- •More than 20 leukemic cells/μL in cerebrospinal fluid;
- •More than 30% leukemic cells in the peripheral blood;
- •Organ recipients;
- •Pregnant or breastfeeding;
- •Active, uncontrolled infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or treponema pallidum (TP).
研究组 & 干预措施
Arm-1: CD19 CAR T and CD22 CAR T-cell sequential treatments (Sequential CAR)
干预措施: CD22 CAR T cells (Drug)
Arm-1: CD19 CAR T and CD22 CAR T-cell sequential treatments (Sequential CAR)
干预措施: CD19 CAR T-cell (Drug)
Arm-2: CD19 CAR T-cell treatment bridging to HSCT (CAR+HSCT)
干预措施: CD19 CAR T-cell (Drug)
Arm-2: CD19 CAR T-cell treatment bridging to HSCT (CAR+HSCT)
干预措施: hematopoietic stem-cell transplantation (Procedure)
结局指标
主要结局
EFS in CD19 CAR and CD22 CAR-T sequential infusion (Sequential CAR group) and CD19 CAR T-cell infusion bridging to HSCT (CAR+HSCT group)
时间窗: 2-year EFS rate
Event-free survival (EFS) of children and adolescent and young adult (AYA) with r/r B-ALL treated with CD19 CAR and CD22 CAR T-cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT. EFS is defined as the time from CD19 CAR T-cell infusion to the earliest relapse, death from any cause, or treatment failure.
次要结局
- DOR in Sequential CAR group and CAR+HSCT group(from enrollment to the end of treatment at 15 years)
- ORR in Sequential CAR group and CAR+HSCT group(3 months (± 1 week) ORR)
- OS in Sequential CAR group and CAR+HSCT group(from enrollment to the end of treatment at 15 years)
- Adverse events (AEs) in Sequential CAR group and CAR+HSCT group(from enrollment to the end of treatment at 2 years)
- Levels of CD19 and CD22 CAR-T cells in Sequential CAR group(from CD19 CAR T-cell infusion to the end of treatment at 15 years)
- Levels of CD19 CAR-T cells in CAR+HSCT group(from CD19 CAR T-cell infusion to the end of treatment at 15 years)
- Levels of CD19 and CD22 CAR transgene in Sequential CAR group(from CD19 CAR T-cell infusion to the end of treatment at 15 years)
- Levels of CD19 CAR transgene in CAR+HSCT group(from CD19 CAR T-cell infusion to the end of treatment at 15 years)
- Quantification of B cells in Sequential CAR group and CAR+HSCT group(from enrollment to the end of treatment at 15 years)
研究者
Jing Pan
Director of Dept of Hemato-Oncology and Immunotherapy
Beijing GoBroad Hospital