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NCT Number: NCT07407140

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

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.

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Key information

Conditions

AML, Adult Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

14 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Primary outcomes

  1. 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

Secondary outcomes

  1. Composite Complete Remission Rate

    Time frame: After induction therapy (approximately 4-8 weeks)

  2. Measurable residual disease-negative CRc rate by flow cytometry

    Time frame: At the time of achieving CRc

    Measurable residual disease-negative CRc rate by flow cytometry after every courses therapy

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

    Time frame: At the time of achieving CRc

    Measurable residual disease-negative CRc rate by NGS for FLT3-ITD after every courses therapy

  4. Relapse-Free Survival (RFS)

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

  5. 30-day and 60-day mortality

    Time frame: 30 and 60 days after start of induction therapy

  6. Overall Survival (OS)

    Time frame: From randomization until death from any cause, assessed up to 3 years

Study contacts

Contact information is provided by the study sponsor or research team.

Hui Wei, MD

CONTACT

[email protected]

13132507161

Sponsors and collaborators

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Other

Registry information

Official study title

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.

Acronym: VAG-3+7-G

Important dates

Study start
2026
Primary completion
2029
Study completion
2030
First posted
Feb 12, 2026
Registry last updated
Mar 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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