Phase I/Ib Clinical Trial of Autologous CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults With Recurrent or Refractory B Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Rate of successful manufacture of CD22 CAR T cells
研究概览
简要总结
The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).
详细描述
Primary Objective:
- Determine the feasibility of manufacturing CD22 CAR T cells using the Miltenyi CliniMACS Prodigy® system for administration to adults with relapsed/refractory CD22 expressing B-cell ALL or relapsed/refractory aggressive B-cell non hodgkins lymphoma (NHL).
- Establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of CD22 CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.
- Determine the safety of an established dose of CD22-CAR T cells in adults with relapsed/refractory CD22 expressing B-cell ALL and the safety of the MTD/RP2D of CD22-CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.
Secondary Objective:
- Assess the clinical activity of CD22-CAR T cells in adults with R/R CD22 expressing B-cell ALL and R/R aggressive B-cell NHL, including overall survival (OS) and progressive free survival (PFS).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
R/R ALL
Relapsed/refractory ALL
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
- Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
- Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10^5cells/kg (± 20%) 10
干预措施: CD22 CAR (Drug)
R/R ALL
Relapsed/refractory ALL
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
- Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
- Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10^5cells/kg (± 20%) 10
干预措施: Fludarabine (Drug)
R/R ALL
Relapsed/refractory ALL
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
- Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
- Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10^5cells/kg (± 20%) 10
干预措施: Cyclophosphamide (Drug)
R/R aggressive B-cell NHL
Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
- Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
- Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D.
Dose1: 1 x 10^6 cells/kg (± 20%) Dose2: 3 x 10^6 cells/kg (± 20%) Dose3: 1 x 10^7 cells/kg (± 20%)
干预措施: Fludarabine (Drug)
R/R aggressive B-cell NHL
Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
- Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
- Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D.
Dose1: 1 x 10^6 cells/kg (± 20%) Dose2: 3 x 10^6 cells/kg (± 20%) Dose3: 1 x 10^7 cells/kg (± 20%)
干预措施: Cyclophosphamide (Drug)
R/R aggressive B-cell NHL
Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
- Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
- Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D.
Dose1: 1 x 10^6 cells/kg (± 20%) Dose2: 3 x 10^6 cells/kg (± 20%) Dose3: 1 x 10^7 cells/kg (± 20%)
干预措施: CD22 CAR (Drug)
结局指标
主要结局
Rate of successful manufacture of CD22 CAR T cells
时间窗: 7-11 days from start of manufacturing
The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells will be determined for each dose cohort.
MTD/RP2D of CD22-CAR T cells in subjects with aggressive B-cell NHL
时间窗: 28 days after infusion of CD22 CAR T cells
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with aggressive B-cell NHL
Safety evaluation of CD22-CAR T cells in subjects with ALL
时间窗: 2 years after infusion of CD22-CAR T cells
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with ALL
次要结局
- Clinical activity of CD22-CAR T cells in adults with relapsed/refractory aggressive B-cell NHL at MTD/RP2D(3 months after infusion of CD22-CAR T cells)
- Clinical activity of CD22-CAR T cells in adults with relapsed/refractory CD22-expressing B-cell ALL at target dose(28 months after infusion of CD22-CAR T cells)