AML, t(8;21), Neoantigen
Conditions
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALtargeted 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 will be performed in -10 to -8d before neoantigen cytotoxic T cells transfusion
Decitabine Injection will be performed in -12 to -8d before neoantigen cytotoxic T cells transfusion
DRUGLiposome mitoxantrone
Liposome mitoxantrone will be performed in -9 to -8d before neoantigen cytotoxic T cells transfusion
Sponsors
Shenzhen University General Hospital
BGI, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | Up to 48 weeks | The total number of subjects with complete response (CR) confirmed and the proportion of subjects in the corresponding analysis set |
| Overall survival (OS) | Up to 72 weeks | The time from cell transfusion to death who have completed the prescribed dose. If the sujects is lost to follow-up, the last known date of surival wil be OS deletion time |
Countries
China
Outcome results
None listed