A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-AIO, a Triple-targeted Cell Preparation Targeting CD19/CD20/CD22, in Patients With Relapsed/Refractory B-cell Acute Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow
研究概览
简要总结
A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LCAR-AIO, a triple-targeted cell preparation targeting CD19/CD20/CD22, in patients with relapsed/refractory B-cell acute lymphocytic leukemia
详细描述
This is an open-label, dose escalation/expansion study to assess the safety, tolerability, and efficacy of LCAR-AIO in patients ≥ 18 years of age with relapsed or refractory B-cell acute lymphocytic leukemia. Patients who meet the eligibility criteria will receive a single dose of LCAR-AIO infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent;
- •Age 18-75 years;
- •ECOG score: 0-1;
- •Detect the expression of at least one of CD19/CD20/CD22 in leukemic cells by Flow cytometry in peripheral blood or bone marrow
- •Leukemia cells in the bone marrow >5%
- •Pathologically confirmed relapsed/refractory ALL must meet one of the following conditions:
- •Naive patients who failed to achieve CR1 after standard chemotherapy;
- •relapse within 12 months after CR1, or relapse after 12 months but fail to achieve CR2
- •twice or more bone marrow relapse
- •Philadelphia chromosomal positive (Ph+) and unable to tolerate TKI therapy, failed TKI therapy more than 2 lines, or had contraindications for TKI therapy
- •Clinical laboratory values meet screening visit criteria
- •Expected survival ≥ 3 months;
排除标准
- •1.Prior antitumor therapy with insufficient washout period; 2.CNS infiltration; Except for patients with prior CNS infiltration who are currently in remission; 3.Have received two or more targets (CD19/CD20/CD22) CAR-T cell therapy (including but not limited to sequential infusion) at any previous time, or have received CAR-T cell therapy from Camel family origin; 4.With acute or chronic graft-versus-host disease; 5.Isolated extramedullary relapse, but hepatic, spleen, or lymph node-isolated extramedullary relapse is acceptable; 6.HBsAg, HBV DNA, HCV-Ab, HCV RNA or HIV-Ab positive; 7.Pregnant or lactating women;
研究组 & 干预措施
LCAR-AIO Cells
Each subject will be treated with LCAR-AIO Cells
干预措施: LCAR-AIO Cells (Biological)
结局指标
主要结局
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow
时间窗: [Time Frame: 2 years after LCAR-AIO infusion (Day 1)]
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow after LCAR-AIO infusion
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment
Recommended Phase 2 dose (RP2D) finding
时间窗: [Time Frame: 30 days after LCAR-AIO infusion (Day 1)]
RP2D established through ATD+BOIN design
次要结局
- Incidence of anti-LCAR-AIO antibody and positive sample titer([Time Frame: Minimum 2 years after LCAR-H93T infusion (Day 1)])
- Overall Survival (OS)([Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)])
- Overall response rate (ORR)([Time Frame: 90 days after LCAR-AIO infusion (Day 1)])
- Duration of Response (DoR)([Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)])
- Time to Response (TTR)([Time Frame: 90 days after LCAR-AIO infusion (Day 1)])
- Relapse-free survival (RFS)([Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)])