Treatment of Relapsed or Refractory t(8; 21) AML With Targeted AML1-ETO Neoantigen Cytotoxic T Cells (CTL)

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

1. 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 .
2. To evaluate the effectiveness of targeted AML1-ETO neoantigen cytotoxic T cells (CTL)，by the complete response rate(CRR) and overall survival (OS) followed.

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.

Inclusion Criteria:

1. Age 18-75 years old (including 18, 75 years old), gender is not limited;
2. 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;
3. The subjects voluntarily participate in the study and sign the Informed Consent Form by themselves or their legal guardians;
4. The HLA types of subjects are HLA-A* 11:01 or HLA-A*02:01;
5. Possessing the AML1-ETO(RUNX1-RUNX1T1) funsion gene;
6. 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 ;
7. No contraindications for collection of mononuclear cells from peripheral blood ;
8. ECOG score ≤1;
9. The survival time is exspected to be≥ 3 months;
10. Have the ability to understand and be willing to sign the informed consent for this test.

Exclusion Criteria:

1. Tumor cells do not express AML1-ETO neoantigen;
2. Active infection;
3. Abnormal liver function [TBil（total bilirubin)>1.5×ULN, ALT>2.5×ULN], abnormal kidney function [Scr（serum creatinine)>1.5×ULN];
4. Unstable angina or 3/4 class of congestive heart failure according to New York Heart Association, or multiple organ dysfunction;
5. HIV/AIDS patients;
6. Participants who need treatment of long-term anticoagulation (warfarin or heparin) or antiplatelet(aspirin>300mg/d; Clopidogrel>75mg/d) ;
7. Participants who received radiotherapy within 4 weeks ,prior to study initiation (blood collection);
8. Known or suspected drug abuse or alcohol dependence;
9. 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;
10. Participants in other clinical trials within 30 days;
11. 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;
12. The investigator evaluates that the subject is unable or unwilling to comply with the requirements of the study protocol;