NCT07407140

VAG Versus Standard Chemotherapy With FLT3 Inhibitor in Adult Patients With FLT3-Mutated AML

A Multicenter, Randomized, Controlled Trial of a Triple-Drug Regimen (Venetoclax, Azacitidine, Gilteritinib) Followed by Intensive Chemotherapy, Versus Standard Chemotherapy Plus Gilteritinib, in Fit Adults With Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia.

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 14 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This study is designed to investigate whether the triplet combination of azacitidine (a hypomethylating agent), venetoclax (a BCL-2 inhibitor), and gilteritinib (a FLT3 inhibitor) as induction therapy improves outcomes compared to standard intensive chemotherapy plus gilteritinib in patients with newly diagnosed FLT3-mutated AML who are fit for intensive chemotherapy.

Conditions

• AML, Adult

Interventions

Type	Name	Description
DRUG	Gilteritinib + Azacitidine + Venetoclax	Patients randomized to this arm receive the novel triplet combination as first-line induction therapy. Patients who achieve complete remission (CR) will receive one repeat cycle of the induction therapy.
DRUG	Cytarabine + Daunorubicin (or Idarubicin) + Gilteritinib	Patients randomized to this arm receive the standard "3+7" intensive chemotherapy plus gilteritinib as the control regimen.
DRUG	Re-induction Therapy	Cytarabine 100 mg/m²/d continuous IV d1-7 or d1-5; Daunorubicin 60 mg/m²/d (or Idarubicin 12 mg/m²/d) IV d1-3 or d1-2; Gilteritinib 120mg d8-21 or d6-19.
DRUG	Consolidation Therapy	Applicable to: All patients achieving CRc (CR/CRh/CRi) following two cycles of induction in the experimental arm or one to two cycles in the control arm. Regimen: Intermediate-dose Cytarabine followed by Gilteritinib per group-specific criteria. Cytarabine (Both Arms): Age \<60 years: 2 g/m² IV q12h, Days 1-3. Age ≥60 years: 1 g/m² IV q12h, Days 1-3. Gilteritinib Addition (120 mg oral, Days 4-17): Control Arm: Administered routinely in all patients. Experimental Arm: Added only if an FLT3 mutation is detectable by NGS-based MRD testing prior to the start of each consolidation cycle.
DRUG	Maintenance Therapy	Applicable to: All patients who have completed consolidation therapy. Experimental Arm: Adjusted-dose VA regimen for 6 cycles. Azacitidine: 75 mg/m²/day, Days 1-7. Venetoclax: 400 mg daily, Days 1-7. Control Arm: Gilteritinib monotherapy for up to 1 year. Gilteritinib: 120 mg daily, Days 1-365.

Timeline

• Start date: 2026-04-30
• Primary completion: 2029-02-01
• Completion: 2030-12-31
• First posted: 2026-02-12
• Last updated: 2026-03-25