This is a multicenter, randomized, controlled, open-label phase III trial evaluating the efficacy and safety of the VAG regimen (azacitidine, venetoclax, and gilteritinib) compared with standard 3+7 chemotherapy (cytarabine plus daunorubicin or idarubicin) combined with gilteritinib in newly diagnosed, fit patients with FLT3-mutated acute myeloid leukemia (AML). A total of 300 patients aged ≥14 to \<75 years with FLT3-ITD or FLT3-TKD mutations will be enrolled and randomized 1:1 to the experimental or control arm, stratified by age (≤60 vs. \>60 years). The primary endpoint is event-free survival (EFS). Secondary endpoints include composite complete remission (CRc) rate, minimal residual disease (MRD) negativity rate by flow cytometry and NGS, overall survival (OS), relapse-free survival (RFS), and 30-day and 60-day mortality.
Newly diagnosed AML (excluding CBF-AML and APL) or MDS/AML (with 10%-20% marrow blasts) per WHO 2022 or ICC criteria
Documented FLT3-ITD or FLT3-TKD mutation by PCR or NGS
Age ≥14 and <75 years
Eligible for intensive chemotherapy
Acute promyelocytic leukemia with PML-RARA
Core-binding factor AML (RUNX1-RUNX1T1 or CBFB-MYH11)
BCR-ABL positive AML
Prior induction chemotherapy for AML (hydroxyurea allowed)