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

March 24, 2026 updated by: Institute of Hematology & Blood Diseases Hospital, China

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
From randomization until treatment failure, relapse after CRc, death from any cause, or last follow-up, assessed up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From randomization until death from any cause, assessed up to 3 years
From randomization until death from any cause, assessed up to 3 years
Composite Complete Remission Rate
Time Frame: After induction therapy (approximately 4-8 weeks)
After induction therapy (approximately 4-8 weeks)
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
At the time of achieving CRc
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
At the time of achieving CRc
Relapse-Free Survival (RFS)
Time Frame: From achievement of CRc until relapse, death, or last follow-up, assessed up to 3 years
From achievement of CRc until relapse, death, or last follow-up, assessed up to 3 years
30-day and 60-day mortality
Time Frame: 30 and 60 days after start of induction therapy
30 and 60 days after start of induction therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institute of Hematology & Blood Diseases Hospital, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 6, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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