Health TrialsbyHealthPanel

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

ConditionAML, Adult
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age14-75
SponsorInstitute of Hematology & Blood Diseases Hospital, China

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

300 Participants
are divided into 2 treatment groups
Group A: VAG Regimen ± VA MaintenanceExperimental treatment 4 interventions
Group B: 3+7 Chemotherapy + GilteritinibActive comparator 4 interventions

Trial outcomes

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

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

Time frame
At the time of achieving CRc
3

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

Time frame
At the time of achieving CRc
4

Relapse-Free Survival (RFS)

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

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute of Hematology & Blood Diseases Hospital, China

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: