NCT06667973

Efficacy of Gilteritinib in Combination With FLAI as Induction Therapy of FLT3-positive Acute Myeloid Leukemia

A Phase 2, Open-label, Multicentre Study Investigating Tolerability and Efficacy of Gilteritinib in Combination With Fludarabine, Cytarabine and Idarubicin (FLAI) as Induction Therapy of Newly Diagnosed Non-M3 FLT3-positive Acute Myeloid Leukemia

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to evaluate the efficacy of gilteritinib as induction therapy in FLT3-positive adult acute myeloid leukemia patients. The main question it aims to answer is: Is gilteritinib in combination to chemotherapy able to improve the complete remission rate of FLT3-positive AML? Participants will receive up to 2 induction cycles with gilteritinib in combination with FLAI (fludarabine, cytarabine, idarubicine) and up to 3 consolidation cycles with gilteritinib and high-dose cytarabine.

Detailed description

This is a multi-center, non-controlled, open-label, Phase 2 interventional study. Young (≤65 years old) patients with newly diagnosed non M3, FLT3-positive acute myeloid leukemia will receive a combination of Gilteritinib and FLAI (fludarabine, high dose cytarabine and idarubicin) as induction treatment. Gilteritinib will be administered at the standard dose of 120 mg which has already been tested in phase I combination trials. (34) Patients failing to achieve CR after first cycle may receive a second identical induction with FLAI. Patients achieving CR after the first cycle of FLAI may receive, upon medical decision, a second induction as well, however omitting fludarabine administration (high dose cytarabine + idarubicin). Consolidation treatment will consist in up to 3 cycles of high dose cytarabine in combination with Gilteritinib. Transplant will be allowed in the trial for eligible patients. The primary endpoint is CR rate after first FLAI (or after second FLAI if administered). Key secondary endpoint is MRD negativity rate after first FLAI (or after second FLAI if administered). As the achievement of CR in AML is required for long term survival, the primary endpoint is of high clinical significance. Furthermore, given the well-known prognostic impact of MRD in CR patients, the key secondary endpoint is also highly relevant. Planned study duration is 60 months. Patient enrollment is expected to be completed in 3 years, and the last patient enrolled will be followed-up for 18 months.

Conditions

• Acute Myeloid Leukemia
• FLT3 Gene Mutation
• Adult AML
• Diagnosis

Interventions

Type	Name	Description
DRUG	Gilteritinib	Gilteritinib fumarate is an oral, selective FLT3 and AXL inhibitor. It is a type 1 inhibitor, active against both the FLT3-ITD and FLT3-TKD mutations. Gilteritinib inhibits FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, FLT3-D835Y, and FLT3-ITD-D835Y, and it induces apoptosis in leukemic cells expressing FLT3-ITD. Gilteritinib is approved for the treatment of relpased/refractory FLT3-mutated AML after the successfull ADMIRAL trial. In the present study Gilteritinib (120 mg/die) in combination with FLAI will be tested as induction therapy in newly-diagnosed patients.

Timeline

• Start date: 2025-06-01
• Primary completion: 2028-08-01
• Completion: 2030-06-01
• First posted: 2024-10-31
• Last updated: 2025-03-12