This is a clinical trial of Anti-FLT3 CAR-T Cell (TAA05 Cell Injection) in the treatment of patients with relapsed / refractory acute myeloid leukemia. The purpose is to evaluate the safety and efficacy of anti-FLT3 CAR-T cells in patients with relapsed / refractory acute myeloid leukemia.
Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal proliferation of hematopoietic stem cells or progenitor cells. AML is the most common type of leukemia in adults; the 5-year survival rate is only 24%. Moreover, 40%-50% of young patients and most elderly patients eventually suffered relapses. FMS-like tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinases, mainly expressed on the cell surface of hematopoietic progenitor cells and plays an important role in normal hematopoiesis such as proliferation, differentiation and survival. The variable expression of FLT3 can be found on leukemia blasts from over 90% of AML patients. Although about 30% of AML have FLT3 gene mutations, the ectodomain of the FLT3 molecule is usually spared so that cellular immunotherapy against it has great therapeutic potential. It is shown that FLT3 expression is detected in more than half of hematopoietic stem cell (HSC) and multipotent progenitor (MPP) cells on average, while the average positive rate of lymphoid progenitor (CLP) cells is less than 20%. Since the expression level of FLT3 on hematopoietic cells is not as high as CD33 and CD123, potential hematological toxicity has been supposed to be less obstructive to the development of FLT3-CAR-T Cell products. Besides, the expression of FLT3 is not found in other normal tissues. And it is reported that FLT3 CAR T cells did not deplete CD34(+) HSCs and preserve HSC differentiation in the mice model. Therefore, conducting CAR-T cell therapy targeting the FLT3 molecule could be very promising in the clinical practice of treating AML. TAA05 Cell Injection is a kind of FLT3-targeted CAR-T cell containing an optimized CD28 costimulatory domain which could help reduce the risk of toxic side effects. This clinical trial aims to evaluate the safety and efficacy of TAA05 Cell Injection in patients with FLT3 positive AML.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Fludarabine + Cyclophosphamide + TAA05 Cell Injection Fludarabine 25 mg/kg \* 3d on day-7\~-2; Cyclophosphamide 250 mg/kg \*3d on day-7\~-2; TAA05 Cell Injection on day 0.
Wuhan Union Hospital
Wuhan, Hubei, China
RECRUITINGMaximal tolerable dose (MTD)
Fludarabine + Cyclophosphamide + TAA05 Cell Injection Patients will receive lymphodepletion with fludarabine (25 mg/kg) and cyclophosphamide (250 mg/kg) for 3 days on day -7\~-2, followed by the infusion of TAA05 Cell with the dose of 1×10\^8, 2×10\^8 or 4×10\^8 cells on day 0. If no dose-limited toxicity(DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. MTD is defined as the highest dose at which DLT occurs in no more than 2 of the 6 patients. After the end of dose climbing, if the maximum dose group(MTD) is still not observed, the highest dose group is defined as MTD.
Time frame: within 2 yeas after infusion
Incidence of Treatment-related Adverse Events
Adverse events will be assessed according to NCI-CTCAE v5.0, cytokine release syndrome and CAR-T cell-related encephalopathy syndrome will be assessed according to ASTCT criteria.
Time frame: within 2 yeas after infusion
Overall response rate(ORR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
OR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 yeas after infusion
Complete response rate(CRR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 yeas after infusion
Overall survival(OS) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
OS will be assessed from CAR T cell infusion to death or last follow-up (censored).
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Masking
NONE
Enrollment
12
Time frame: within 2 yeas after infusion
Progress-free survival(PFS) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 yeas after infusion
Duration of Response(DOR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 yeas after infusion
In vivo expansion and survival of Anti-FLT3 CAR-T Cell
Quantity of CAR copies in bone marrow and peripheral blood will be determined by using qPCR.
Time frame: within 2 yeas after infusion