targeted AML1-ETO neoantigen cytotoxic T cells (CTL)Cyclophosphamide injectionDecitabine InjectionLiposome mitoxantrone
targeted AML1-ETO neoantigen cytotoxic T cells (CTL): After subject screening, peripheral blood mononuclear cell #PBMC# donors matching half or more of the subject's HLA matching will undergo blood collection to prepare neoantigen cytotoxic T cells. Neoantigen cytotoxic T cells preparation is expected to be 25-30 days after blood collection. In this study, the bridging therapy will be allowed before Chemotherapy preconditioning. Chemotherapy preconditioning will be performed before neoantigen cytotoxic T cells transfusion.
Cyclophosphamide injection: Cyclophosphamide injection will be performed in -10 to -8d before neoantigen cytotoxic T cells transfusion
Decitabine Injection: Decitabine Injection will be performed in -12 to -8d before neoantigen cytotoxic T cells transfusion
Liposome mitoxantrone: Liposome mitoxantrone will be performed in -9 to -8d before neoantigen cytotoxic T cells transfusion
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
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;
Primary outcome measure(s)
Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0) — 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
Trial sites (1)
Facility
City
Region
Status
Shenzhen University General Hospital
Shenzhen
Guangdong
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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