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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
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
Shenzhen University General Hospital
Shenzhen, Guangdong, China
Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)
To determine the incidence of AE and SAE in clinical trials
Time frame: 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.
Complete response rate
The total number of subjects with complete response (CR) confirmed and the proportion of subjects in the corresponding analysis set
Time frame: Up to 48 weeks
Overall survival (OS)
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
Time frame: Up to 72 weeks
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Decitabine Injection will be performed in -12 to -8d before neoantigen cytotoxic T cells transfusion
Liposome mitoxantrone will be performed in -9 to -8d before neoantigen cytotoxic T cells transfusion