A Clinical Study to Evaluate the Safety and Initial Efficacy of Targeted AML1-ETO Neoantigen Cytotoxic T Cells (CTL) in the Treatment of Relapsed or Refractory t(8; 21) AML
试验速览
- 阶段
- 早期 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)
研究概览
简要总结
- To evaluate the safety and tolerability of targeted AML1-ETO neoantigen cytotoxic T cells (CTL) in the treatment of relapsed or refractory acute myeloid leukemia .
- To evaluate the effectiveness of targeted AML1-ETO neoantigen cytotoxic T cells (CTL)，by the complete response rate(CRR) and overall survival (OS) followed.
详细描述
This is a single arm、open label and non-randomied clinical trial ，divided into dose exploration phase (Part A) and dose extension phase (Part B).
Part A: Plan to enroll six subjects to evaluate the safety and tolerabilty of targeted neoantigen cytotoxic T cells (CTL),determine dose-limiting toxicity(DLT),explore the maximum tolerated dose (MTD) or the recommended dose for later clilnical studies.The DLT observation period is 28 days after the infusion of targeted neoantigen cytotoxic T cells (CTL) iniection. One dose group(total number of cells is 5×10^7/bag) and the another one (total number of cells is 10×10^7 /bag )is setted by the 3+3 test design.
Part B: Ten subjects are planned to be enrolled in the dose-exploration phase with the recommended dose, to further evaluate the safety、tolerability and its efficacy of targeted neoantigen cytotoxic T cells (CTL) in relapsed or refractory acute myeloid leukemia.
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
- •Age 18-75 years old (including 18, 75 years old), gender is not limited;
- •According to WHO (2020) criteria, the subjects are diagnosed for recurrent or refractory t(8:21) acute myeloid leukemia or demonstrated persistant AML1-ETO positiving or genetic MRD recurrence after ≥3 cycles of intensive chemotherapy, as confirmed by quantitative PCR;
- •The subjects voluntarily participate in the study and sign the Informed Consent Form by themselves or their legal guardians;
- •The HLA types of subjects are HLA-A* 11:01 or HLA-A*02:01;
- •Possessing the AML1-ETO(RUNX1-RUNX1T1) funsion gene;
- •Disease progression after adequate first-line systemic treatment for remission, or disease progression after first-line or above systemic systemic treatment for ≥2 cycles , or without remission (CR or PR) after≥4 cycles of treatment ;
- •No contraindications for collection of mononuclear cells from peripheral blood ;
- •ECOG score ≤1;
- •The survival time is exspected to be≥ 3 months;
- •Have the ability to understand and be willing to sign the informed consent for this test.
排除标准
- •Tumor cells do not express AML1-ETO neoantigen;
- •Active infection;
- •Abnormal liver function [TBil（total bilirubin)>1.5×ULN, ALT>2.5×ULN], abnormal kidney function [Scr（serum creatinine)>1.5×ULN];
- •Unstable angina or 3/4 class of congestive heart failure according to New York Heart Association, or multiple organ dysfunction;
- •HIV/AIDS patients;
- •Participants who need treatment of long-term anticoagulation (warfarin or heparin) or antiplatelet(aspirin>300mg/d; Clopidogrel>75mg/d) ;
- •Participants who received radiotherapy within 4 weeks ,prior to study initiation (blood collection);
- •Known or suspected drug abuse or alcohol dependence;
- •Patients with mental disorders or other medical conditions are unable to obtain informed consent and cooperate to complete the requirements of experimental treatment and examination procedures;
- •Participants in other clinical trials within 30 days;
- •Pregnant or lactating women and male subjects (or their partners) or female subjects who plan to become pregnant during the study period and within 6 months after the end of the study ,and do not wish to use a medically approved effective contraceptive method (such as an IUD or condom) during the study period;
- •The investigator evaluates that the subject is unable or unwilling to comply with the requirements of the study protocol;
研究组 & 干预措施
targeted AML1-ETO neoantigen cytotoxic T cells (CTL)
The escalating doses of cells (CTL) in this study will be 5*10^7 cells and 1*10^8 cells.
干预措施: targeted AML1-ETO neoantigen cytotoxic T cells (CTL) (Biological)
targeted AML1-ETO neoantigen cytotoxic T cells (CTL)
The escalating doses of cells (CTL) in this study will be 5*10^7 cells and 1*10^8 cells.
干预措施: Cyclophosphamide injection (Drug)
targeted AML1-ETO neoantigen cytotoxic T cells (CTL)
The escalating doses of cells (CTL) in this study will be 5*10^7 cells and 1*10^8 cells.
干预措施: Decitabine Injection (Drug)
targeted AML1-ETO neoantigen cytotoxic T cells (CTL)
The escalating doses of cells (CTL) in this study will be 5*10^7 cells and 1*10^8 cells.
干预措施: Liposome mitoxantrone (Drug)
结局指标
主要结局
Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)
时间窗: From preconditioning or cell reinfusion to one year after cell reinfusion or the initiation of other antitumor therapy or the discontinuation of the trial for other reasons, whichever occurred first.
To determine the incidence of AE and SAE in clinical trials
次要结局
- Complete response rate(Up to 48 weeks)
- Overall survival (OS)(Up to 72 weeks)