NCT06561880

The Efficacy of Triple Regimen in Newly Diagnosed AML Patients With FLT3 Mutation

A Multi-center, Single-arm Trial of the Efficacy of a Triple Regimen Including Gilteritinib, Venetoclax, and Azacitidine in Newly Diagnosed Fit AML Patients With FLT3 Mutation

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 14 Years
• Healthy volunteers: Not accepted

Summary

The FMS tyrosine kinase 3 (FLT3) gene mutation occurs in 30% of newly diagnosed AML patients, leading to a higher relapse rate and mortality rate. In the past, multi-drug combination chemotherapy regimens had limited efficacy in newly diagnosed AML patients with FLT3 mutations, especially in those with FLT3-ITD. However, the FLT3 inhibitors greatly improved the survival of AML patients with FLT3 mutations. Although several studies have focused on the effectiveness of FLT3 inhibitor combination therapy for FLT3-mutated AML, further studies are needed to determine the optimal regimen and dosage. A triple regimen consisting of Gilteritinib, Venetoclax, and Azacitidine had shown good efficacy in unfit newly diagnosed FLT3-mutated AML patients. This clinical trial aims to determine the optimal dosage of the triple regimen and investigate its efficacy in newly diagnosed fit FLT3-mutated AML patients. Besides, this trial will provide evidence for treatment decisions based on measurable residual disease in patients with the triple regimen.

Detailed description

This stuay intends to conduct a multi-center, single-arm clinical study to explore the efficacy of the triple induction regimen consisting of Gilteritinib, Venetoclax, and Azacitidine in newly diagnosed FLT3 mutated AML patients who are suitable for intensive chemotherapy. The maximum dose of Gilteritinib that can be safely combined with Azacitidine and Venetoclax will be determined. Patients will receive 2 courses of a triple regimen therapy for induction and those who achieved complete remission will receive 3 courses of intermediate-dose cytarabine for consolidation. After consolidation therapy, dose-adjusted triple regimen therapy will be applied for 6 courses as maintenance treatment. Bone marrow morphology and minimal residual disease detected by flow cytometry and next-generation sequencing will be monitored during the treatment to provide evidence for treatment decisions. Response and survival of patients will be recorded to evaluate the efficacy of the triple regimen.

Conditions

• FLT3 Gene Mutation
• AML

Interventions

Type	Name	Description
DRUG	Gilteritinib	Induction therapy regimen(2 courses): triple regimen therapy: Azacitidine 75mg/m2/d d1-7; Venetoclax 100mg d1,200mg d2,400mg d3-28; Gilteritinib (as required at admission: 80 or 120mg) d1-28. dose-adjusted triple regimen therapy: Azacitidine 75mg/m2/d d1-5; Venetoclax 400mg d1-7; Gilteritinib (as required at admission: 80 or 120mg) d1-28. Patients with no remission after the first induction course will receive another course with triple regimen therapy; Patients with complete remission after the first induction course will receive another course of dose-adjusted triple regimen therapy.
DRUG	Cytarabine	Consolidation therapy (3 courses): intermediate-dose cytarabine regimen :2g/m2 q12h d1-3, age \< 60 years;1g/m2 q12h d1-3, age ≥60 years. If NGS detected FLT3 mutation before consolidation chemotherapy, gilteritinib will be added during the consolidation course at d4-17.
DRUG	Gilteritinib	Maintenance treatment (6 courses): dose-adjusted triple regimen therapy:Azacitidine 75mg/m2/d d1-5; Venetoclax 400mg d1-7; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

Timeline

• Start date: 2024-10-08
• Primary completion: 2026-09-01
• Completion: 2027-08-31
• First posted: 2024-08-20
• Last updated: 2025-10-01

Locations

1 site across 1 country: China