VAG Versus Standard Chemotherapy With FLT3 Inhibitor in Adult Patients With FLT3-Mutated AML (VAG-3+7-G)

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: AML, Adult
• Intervention / Treatment: Drug: Gilteritinib + Azacitidine + Venetoclax; Drug: Consolidation Therapy; Drug: Maintenance Therapy; Drug: Cytarabine + Daunorubicin (or Idarubicin) + Gilteritinib; Drug: Re-induction Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hui Wei, MD; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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: 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.; 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.
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.	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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		From randomization until death from any cause, assessed up to 3 years
Composite Complete Remission Rate		After induction therapy (approximately 4-8 weeks)
Measurable residual disease-negative CRc rate by flow cytometry	Measurable residual disease-negative CRc rate by flow cytometry after every courses therapy	At the time of achieving CRc
Measurable residual disease-negative CRc rate by NGS for FLT3-ITD	Measurable residual disease-negative CRc rate by NGS for FLT3-ITD after every courses therapy	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 6, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Health Care Facilities Workforce and Services; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Cytarabine; Azacitidine; Daunorubicin; Idarubicin; venetoclax; gilteritinib; Maintenance
• Other Study ID Numbers: IIT2026012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No