Clinical Study on the Safety and Effectiveness of CLL1 CAR-T Cells in the Treatment of CLL1-positive Hematological Malignancies
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
Clinical Study on the Safety and Effectiveness of CLL1 CAR-T Cells in the Treatment of CLL1-positive Hematological Malignancies
详细描述
Human C-type lectin-like molecule 1 (CLL1) is a type II transmembrane glycoprotein ，CLL1 expression is restricted to bone marrow cells and most AML blasts. In addition, CLL1 is expressed in leukemia stem cells (LSC) but not in hematopoietic stem cells (HSC), may provide a potential therapeutic target for the treatment of AML.The CAR-T cell injection uses immune cells from healthy donors, and is the final product obtained after CAR genetic modification, cell expansion, culture, screening, preparation, sub-packaging, and release inspection. The center intends to apply for a clinical trial of CLL1 CAR-T cells to treat CLL1-positive hematological malignancies on the basis of preliminary research.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients is histologically diagnosed with CLL1-positive AML according to the NCCN Clinical Practice Guidelines in Oncology：Acute Myeloid Leukemia（Version 2.2021）
- •The diagnosis is consistent with r/r CLL1 + AML, and includes any of the following conditions:
- •No CR was obtained after 2 courses of standard chemotherapy
- •The first induction was CR, but the duration of CR was less than 12 months
- •No CR was obtained after the first or multiple remedial treatment;
- •Relapse twice or more;
- •The number of blast cells in bone marrow was more than 5% (morphology) and / or > 1% (flow cytometry).
- •No active lung infection, inhaled air oxygen saturation ≥92%
- •The estimated survival time is more than 3 months
- •ECOG score was 0-2
- •The patients or their legal guardians voluntarily participated in the trial and signed the informed consent.
排除标准
- •Patients with history of epilepsy or other central nervous system diseases;
- •Patients with prolonged QT or severe heart disease;
- •Pregnant or lactating women (the safety of this therapy for unborn children is unknown);
- •The patients with uncontrolled active infection;
- •Active hepatitis B or hepatitis C virus infection;
- •Previous application of gene therapy;
- •The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
- •Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl;
- •Those who suffer from other uncontrolled diseases are not suitable to join the study;
- •HIV infection;
- •Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: Baseline up to 28 days after CLL1 CAR T-cells infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 90 days after CLL1 CAR T-cells infusion
Incidence of treatment-emergent adverse events \[Safety and Tolerability\]
次要结局
- Progression-free survival, PFS(24 months post CLL1 CAR-Tcells infusion)
- Overall survival, OS(From CLL1 CAR-T infusion to death,up to 2 years)
- Concentration of CAR-T cells(From admission to the end of the follow-up, up to 2 years)
- Disease control rate, DCR(From Day 28 CLL1 CAR-T infusion up to 2 years)
- Duration of remission, DOR(24 months post CLL1 CAR-T cells infusion)
研究者
He Huang
The President of The First Affiliated Hospital, College of Medicine, Zhejiang University
Zhejiang University