VAG Versus Standard Chemotherapy With FLT3 Inhibitor in Adult Patients With FLT3-Mutated AML
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Gilteritinib + Azacitidine + Venetoclax, Cytarabine + Daunorubicin (or Idarubicin) + Gilteritinib, Re-induction Therapy, Consolidation Therapy.
- Who it may be relevant to
- Registry conditions: AML, Adult. Basic parameters: 14 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official 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.
Overview
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.
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.
Interventions
- 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 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. - 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 m - 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.
Primary outcome measures
- 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 outcome measures (6)
- Composite Complete Remission Rate [Time frame: 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 NGS for FLT3-ITD [Time frame: 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]
- 30-day and 60-day mortality [Time frame: 30 and 60 days after start of induction therapy]
- Overall Survival (OS) [Time frame: From randomization until death from any cause, assessed up to 3 years]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07407140 · IIT2026012