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

NCT07407140 | Not Yet Recruiting Phase 3

• 1 other identifier: IIT2026012
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

AML, Adult

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  From randomization until treatment failure, relapse after CRc, death from any cause, or last follow-up, assessed up to 3 years

Secondary Outcomes (6)

• Composite Complete Remission Rate

  After induction therapy (approximately 4-8 weeks)

• Measurable residual disease-negative CRc rate by flow cytometry

  At the time of achieving CRc

• Measurable residual disease-negative CRc rate by NGS for FLT3-ITD

  At the time of achieving CRc

• Relapse-Free Survival (RFS)

  From achievement of CRc until relapse, death, or last follow-up, assessed up to 3 years

• 30-day and 60-day mortality

  30 and 60 days after start of induction therapy

Study Arms (2)

VAG Regimen ± VA Maintenance

EXPERIMENTAL

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.

Drug: Gilteritinib + Azacitidine + Venetoclax; Drug: Re-induction Therapy; Drug: Consolidation Therapy; Drug: Maintenance Therapy

3+7 Chemotherapy + Gilteritinib

ACTIVE COMPARATOR

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.

Drug: Cytarabine + Daunorubicin (or Idarubicin) + Gilteritinib; Drug: Re-induction Therapy; Drug: Consolidation Therapy; Drug: Maintenance Therapy

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.

VAG Regimen ± VA Maintenance

Cytarabine + Daunorubicin (or Idarubicin) + Gilteritinib DRUG

Patients randomized to this arm receive the standard "3+7" intensive chemotherapy plus gilteritinib as the control regimen.

3+7 Chemotherapy + Gilteritinib

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.

3+7 Chemotherapy + Gilteritinib; VAG Regimen ± VA Maintenance

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.

3+7 Chemotherapy + Gilteritinib; VAG Regimen ± VA Maintenance

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.

3+7 Chemotherapy + Gilteritinib; VAG Regimen ± VA Maintenance

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ECOG performance status 0-2
• Adequate organ function (liver, kidney, cardiac)
• Written informed consent

You may not qualify if:

• 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)
• Concurrent active malignancy requiring therapy
• Active/symptomatic cardiac disease
• Severe uncontrolled infection
• Any condition deemed unsuitable by the investigator

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; Azacitidine; venetoclax; Cytarabine; Daunorubicin; Idarubicin; Maintenance

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Health Care Facilities Workforce and Services

Central Study Contacts

Hui Wei, MD

CONTACT

13132507161; weihui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: February 12, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 25, 2026

Record last verified: 2026-03