NCT07425808

FLT3-ITD Targeted Therapy in Fit AML Patients

Gilteritinib in Combination With Azacitidine and Venetoclax Compared to Induction Chemotherapy "7+3" in Combination With a FLT3-inhibitor in Fit, Newly Diagnosed, FLT3-ITD Mutated Adult AML Patients: a Randomized Trial of the EORTC Leukemia Group and GIMEMA.

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 230 (estimated)
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC · Network
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This international, multicenter, randomized (1:1), open-label phase II/III trial will evaluate the efficacy and safety of gilteritinib combined with azacitidine and venetoclax (experimental arm) versus standard "7+3" induction plus a FLT3inhibitor (quizartinib or midostaurin) (control arm) in newly diagnosed FLT3-ITD mutated AML patients eligible for intensive chemotherapy.

Detailed description

Newly diagnosed AML patients deemed fit by the investigator to receive intensive chemotherapy will be screened for FLT3-ITD mutation. Eligible patients will be randomized in a 1:1 ratio between experimental and control arms, stratified by age and WBC at diagnosis: * Participants assigned to the experimental arm will receive a triplet regimen consisting of VEN, AZA, and gilteritinib, administered for up to 12 cycles. This will be followed by up to 12 additional cycles of AZA in combination with gilteritinib, and subsequently up to 12 cycles of gilteritinib monotherapy * Participants in the control arm will be treated following the local standard of care, consisting of induction with '7+3', consolidation with high-dose cytarabine, and maintenance with a FLT3 inhibitor (midostaurin, quizartinib, or sorafenib) as per local practice. Participants in the experimental arm with an available donor should proceed to HSCT based on the local investigator's judgement, but this should not occur prior to the end of cycle 2. For participants in the control group, HSCT is as per the local investigator's judgement, but recommended in first CR/CRi. For patients with no available donor and not proceeding to HSCT, treatment in the experimental arm is recommended to continue for a minimum of 6 cycles before transitioning to maintenance treatment with AZA and gilteritinib. Following HSCT, patients in the experimental arm will receive gilteritinib maintenance for up to 36 cycles and in the control arm, FLT3-inhibitor as per local standard of care (i.e., midostaurin, quizartinib or sorafenib).

Conditions

• AML (Acute Myeloid Leukemia)

Interventions

Type	Name	Description
DRUG	Gilteritinib	Cycle 1: 80 mg once daily orally on days 1-28. Cycle 2 - 12: 80mg once daily orally on days 1-28. Cycle 13 - 24: gilteritinib 120 mg once daily orally on days 1-28. Following HSCT, maintenance with gilteritinib (120 mg once daily orally on days 1-28) will be offered for up to 36 cycles and started between day 30 and 90 after hematopoietic stem-cell transplantation (HSCT).
DRUG	Venetoclax	Cycle 1: ramp-up from 100mg on day 1, 200 mg on day 2 and 400 mg on days 3 - 28. Cycle 2 - 12: venetoclax 400 mg once daily orally days 1-7.
DRUG	Azacitidine (AZA)	Cycle 1: 75 mg/m² once daily subcutaneously on days 1-7. Cycle 2 -12: 75 mg/m² once daily subcutaneously on days 1-5. Cycle 13 - 24: 75 mg/m² once daily subcutaneously on days 1-5.
DRUG	Local standard of care (SOC)	Local SOC is "7+3" + Midostaurin (100 mg) or Quizartinib (35.4 mg)

Timeline

• Start date: 2026-12-01
• Primary completion: 2028-10-01
• Completion: 2032-02-01
• First posted: 2026-02-23
• Last updated: 2026-02-23