This is a single arm , open-label, dose-escalation clinical study with the primary objective of evaluating the safety and tolerability of TAA05 injection in adult subjects with FLT3-positive relapsed/refractory acute myeloid leukemia. The secondary objectives are as follows: to evaluate the in vivo expansion and persistence of FLT3-targeted chimeric antigen receptor T (CAR-T) cells after injection of TAA05;to evaluate the proportion of FLT3-positive cells in peripheral blood after injection of TAA05;to preliminarily evaluate the efficacy of TAA05 injection in adult subjects with FLT3-positive relapsed/refractory acute myeloid leukemia;to evaluate the immunogenicity of TAA05 injection;and to explore the applicable dose in the formal clinical phase.
Approximately 1 sites are planned to be selected for the clinical trial. The subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be assigned into 1.0 × 10\^8, 2.0 × 10\^8 and 4.0 × 10\^8 CAR-T groups in order of sequence. And the subjects will be administered once. Dose escalation will follow 3 + 3 design and 3-6 subjects in each group will complete a single dose. Within the same dose group, the next subject will be administered after the previous subject has completed at least 14 days of safety observation. After the last subject in each dose group has completed the dose-limiting toxicity (DLT) assessment window of 28 days after single dose, the enrollment and treatment for the next dose group may be initiated after the Safety Review Committee (SRC) agrees to enter the next dose group based on clinical safety data assessment. When DLT occurs in 1 of 3 subjects in a dose group, 3 additional subjects in the same dose group will be required (up to 6 subjects in the dose group have completed DLT assessment): if no DLT occurs in the additional 3 subjects, dose escalation will continue; if 1 of the 3 additional subjects experiences one DLT, dose escalation will be discontinued; if more than 1 of the 3 additional subjects experiences DLTs, dose escalation will be discontinued, and 3 additional subjects will be required to be enrolled at one lower dose level for DLT assessment. After the end of escalation for the maximum dose group, if no MTD is observed, the highest dose level is defined as the MTD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
The subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be assigned into 1.0 × 10\^8, 2.0 × 10\^8 and 4.0 × 10\^8 CAR-T groups in order of sequence. And the subjects will be administered once.
Union Hospital, affiliated with TongJi Medical College, HuaZhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGDLT
Dose limiting toxicity
Time frame: About 2 years
MTD
Maximum tolerated dose
Time frame: About 2 years
Assessment of the safety after FLT3-targeted chimeric antigen receptor T cells infusion (Safety)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Time frame: About 2 years
Assessment of pharmacokinetic (about Cmax)
Assessment of the highest concentration (Cmax) of FLT3-targeted chimeric antigen receptor T cells amplified in peripheral blood after administration.
Time frame: About 28 days
Assessment of pharmacokinetic (about Tmax)
Assessment of the time to reach the highest concentration (Tmax) of FLT3-targeted chimeric antigen receptor T cells amplified in peripheral blood after administration.
Time frame: About 28 days
Assessment of pharmacokinetic (about AUC0-28d)
Assessment of the area under the curve AUC0-28d after administration.
Time frame: About 28 days
Assessment of pharmacokinetic (about AUC0-90d)
Assessment of the area under the curve AUC0-90d after administration. Assessment of the area under the curve AUC0-90d after administration. Assessment of the area under the curve AUC0-90d after administration.
Time frame: About 90 days
PD endpoints
The proportion and absolute value of FLT3-positive cells in peripheral blood at each time point; concentration levels of CAR-T-related serum cytokines such as CRP and IL-6.
Time frame: About 2 years
To Evaluate Anti-tumour Activity (overall response rate)
Rate of participants who with lymphoma aquire complete response (CR) or partial response (PR) or those who with leukemia CR or CR with incomplete hematologic recovery (CRi).
Time frame: About 3 months
To Evaluate Anti-tumour Activity (Overall Survival)
Defined as the time from start of FLT3 CAR-T cell therapy to death (due to any cause)
Time frame: About 2 years
To Evaluate Anti-tumour Activity (duration of response)
Defined as the time from the first tumor assessment of CR or PR , CR or CRi to the first assessment of disease recurrence or progression or death (due to any cause).
Time frame: About 2 years
To Evaluate Anti-tumour Activity (Progression Free Survival)
Defined as the time from the start of FLT3 CAR-T cell therapy to the first disease progression or recurrence or death from any cause.
Time frame: About 2 years
Immunogenicity endpoints
Positive rate of human anti-CAR antibody at each time point.
Time frame: About 2 years
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