Safety, Tolerability and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allogeneic Haematopoietic Stem Cell Transplantation and Sequential Donor-derived CD22 CAR Therapy in Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia: a Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Adverse events (AEs)
研究概览
简要总结
This is an investigator-initiated, single-arm, open-label, non-randomised phase I clinical study. The objective of this trial is to evaluate the safety, tolerability and pharmacokinetics of donor-derived CD19 CAR Therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR Therapy for r/r B-ALL and to explore the efficacy of this therapy preliminarily. The primary endpoints are incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridged allogeneic haematopoietic stem cell transplantation; total number, incidence and severity of adverse events from donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T cell infusion). The secondary endpoints are total number, incidence and severity of adverse events from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion; ORR(CR+CRi) on days 45, 90, 120; duration of response(DOR), event-free survival(EFS), overall survival(OS); pharmacokinetics characteristics. The trial plan to enroll 3~12 cases in dose escalation phase and 36 cases in dose expansion phase.
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
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Patients will be enrolled only if they meet all the inclusion criteria.
- •Patients with relapsed or refractory CD19+/CD22+ (FCM >95%) B-cell acute lymphoblastic leukaemia who have progressed despite or are intolerant to all standard therapies, including, but not limited to, immunotherapies such as Blinatumomab (BITE), Tyrosine kinase inhibitors (TKI), CAR T-cell therapy, etc.; Currently available therapies have a limited prognosis and there are no available curative treatment options (e.g., HSCT or chemotherapy);
- •Peripheral blood tumour burden ≥60% or severe peripheral blood cytopenia, unsuitable/unable to collect autologous lymphocytes;
- •1 to 18 years old;
- •Patient's expected survival time ≥ 60 days;
- •Physical status: ECOG score 0-2;
- •Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;
- •Sign an informed consent form during the screening period. Pediatric patients under 8~18 years of age need to have sufficient awareness to voluntarily sign an informed consent form, and their legal representatives (guardians) also need to voluntarily sign an informed consent form; pediatric patients aged 1~7 years can only be recruited after their legal guardians have voluntarily signed an informed consent form.
排除标准
- •Patients who meet any of the following criteria are not eligible for enrolment.
- •Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);
- •Intracranial hypertension or cerebral impaired consciousness;
- •Symptomatic heart failure or severe cardiac arrhythmia;
- •Symptoms of severe respiratory failure;
- •With other types of malignant tumours;
- •Diffuse intravascular coagulation;
- •Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
- •Suffering from sepsis or other uncontrollable infections;
- •Suffering from uncontrollable diabetes mellitus;
- •Severe mental disorders;
- •Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);
- •Have organ transplant history;
- •Female patients (patients of childbearing potential) with positive blood HCG test;
- •Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;
- •No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.
研究组 & 干预措施
Arm-1
Participants receive donor-derived CD19 CAR therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR therapy
干预措施: Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy (Drug)
结局指标
主要结局
Adverse events (AEs)
时间窗: Within 120 days of donor-derived CD19 CAR T-cell infusion
Total number, incidence and severity of adverse events (AEs) from the time of donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T-cell infusion) will be recorded.
Dose-limiting toxicity (DLT)
时间窗: Within 43 days of donor-derived CD19 CAR T-cell infusion
Incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridging allogeneic haematopoietic stem cell transplantation will be recorded.
次要结局
- Long-term Adverse events (AEs)(From 120 days to 2 years after donor-derived CD19 CAR T-cell infusion)
- Objective response rate(ORR)(day 30, day 45, day 90)
- Duration of response (DOR)(Up to 2 years)
- Event-free survival (EFS)(Up to 2 years)
- The Maximum concentration (Cmax) of CD19/CD22 CAR T cells.(Up to 2 years)
- The persistence of CD19/CD22 CAR T cells.(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- The time to maximum plasma concentration (Tmax) of CD19/CD22 CAR T cells.(Up to 2 years)
研究者
Jing Pan
Director of Dept of Hemato-Oncology and Immunotherapy
Beijing GoBroad Hospital