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

Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Study ID
NCT07407140
Phase
PHASE3
Status
Not Yet Recruiting

Notify me when recruiting opens

Save your spot on the interest list for this study. We'll keep your details with this study so our team can follow up when recruiting opens.

Not yet recruiting

Add your contact details and location so we can keep your interest tied to this study.

Conditions

  • AML, Adult

Eligibility Criteria

Sex
ALL
Age
14 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Gilteritinib + Azacitidine + Venetoclax — DRUG
    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.
  • Cytarabine + Daunorubicin (or Idarubicin) + Gilteritinib — DRUG
    Patients randomized to this arm receive the standard "3+7" intensive chemotherapy plus gilteritinib as the control regimen.
  • Re-induction Therapy — DRUG
    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.
  • Consolidation Therapy — DRUG
    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.
  • Maintenance Therapy — DRUG
    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.

Study Details

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.

Key Dates

Start date
Apr 30, 2026
Status verified
Mar 2026
Primary completion
Feb 1, 2029
Completion
Dec 31, 2030

Study Design

Enrollment
300 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: VAG Regimen ± VA Maintenance
    Induction (Age \<60): Azacitidine 75 mg/m²/d d1-7; Venetoclax 100mg d1, 200mg d2, 400mg d3-14; Gilteritinib 120mg d1-14. Bone marrow assessment on d14: if blasts \>5% with active marrow, Gilteritinib and Venetoclax may extend to d21. Induction (Age ≥60): Azacitidine 75 mg/m²/d d1-7; Venetoclax 100mg d1, 200mg d2, 400mg d3-7; Gilteritinib 120mg d1-7. Bone marrow assessment on d7: if blasts \>5% with active marrow, Gilteritinib and Venetoclax may extend to d14. Re-induction (if not CR/CRh/CRi): Gilteritinib 80mg d1-28; Azacitidine 75 mg/m²/d d1-7; Venetoclax 100mg d1, 200mg d2, 400mg d3-14 (extend to d21 if d14 blasts \>5%). Consolidation (after CR): Azacitidine 75 mg/m²/d d1-5; Venetoclax 400mg d1-14; Gilteritinib 120mg d1-14. For 2 cycles. Maintenance: Azacitidine 75 mg/m²/d d1-5; Venetoclax 400mg d1-7. For 6 cycles.
  • Active Comparator: 3+7 Chemotherapy + Gilteritinib
    Induction: Cytarabine 100 mg/m²/d continuous IV d1-7; Daunorubicin 60 mg/m²/d (or Idarubicin 12 mg/m²/d) IV d1-3; Gilteritinib 120mg d8-21. Re-induction (if not CR/CRh/CRi): 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. Consolidation (after CR): Intermediate-dose Cytarabine 2 g/m² (age \<60) or 1 g/m² (age ≥60) q12h d1-3; Gilteritinib 120mg d4-17. For 3 cycles. Maintenance: Gilteritinib 120mg daily. For up to 365 days.

Primary Outcome Measure

Event-Free Survival (EFS) [ Time Frame: From randomization until treatment failure, relapse after CRc, death from any cause, or last follow-up, assessed up to 3 years ]

Central Contacts

Related Studies