NCT07028073

A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia

Avapritinib Combined With Standard Therapy for the Treatment of Newly Diagnosed KIT Mutation Acute Myeloid Leukemia With t(8;21)(q22;q22.1); Inv(16)(p13.1q22) or t(16;16)(p13.1;q22): a Prospective, Multi-center, Single-arm, Two-cohorts Study

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Sponsor: The First Affiliated Hospital of Soochow University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if avapritinib combined with standard induction therapy works to treat newly diagnosed adult acute myeloid leukemia (AML) patients with KIT mutations and t(8;21)(q22;q22.1); inv(16)(p13.1q22) or t(16;16)(p13.1;q22). It will also investigate the safety and tolerability of this combination therapy. The main questions it aims to answer are: To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of avapritinib combined with chemotherapy by Dose-limiting toxicity (DLT). Does this combination therapy improve the rates of minimal residual disease (MRD) negativity and long-term survival outcomes?

Detailed description

The prognosis of CBF-AML patients with KIT mutation remains relatively poor. CBF-AML is a heterogeneous disease in which many altered molecular pathways could contribute to the prognosis of the disease. Thus, curative approaches have been based on standard and high-dose cytarabine regimens using high-dose chemotherapy. However, the high rate of relapses in these patients should stimulate the development of new regimens. In recent years, there has been a series of new drugs under development that allow the design of combination therapies in this population. These drugs have an acceptable toxicity profile and are able to improve the CR rate in this population. In this way, the standard therapy and a small molecular targeted agent (Avapritinib) could produce a powerful antileukemic effect, preventing the adaptive escape mechanisms of leukemic cells. The investigators have designed a phase I-II trial based on the combination of a three-drug regimen (IA: standard-dose cytarabine + darubicin) or (VA: Azacitidine + Venetoclax) combined with avapritinib, which in this population could be well tolerated by a sequential type administration. The first objective is to achieve rapid control of the disease and the recommended dose for Phase II, using two different schemes, one based on IA and the other on VA, by dose escalation in Phase I of the trial. The second goal is to prevent relapse through a consolidation and maintenance schedule. Phase II will study the efficacy and safety of the recommended dose for Phase II.

Conditions

• Acute Myeloid Leukemia With T(8;21)(Q22;Q22)
• Acute Myeloid Leukemia With T(16;16)(P13;Q22)
• KIT Gene Mutation
• Avapritinib

Interventions

Type	Name	Description
DRUG	Group A (FIT): Avapritinib + IA regimen	Cytarabine 100mg/m² days 1-7 Idarubicin 12mg/m² days 1-3 Avapritinib orally on days 8-21 (28-day cycle)
DRUG	Group B (UNFIT): Avapritinib + VA regimen	Venetoclax 100mg day 1, 200mg day 2, 400mg days 3-28 Azacitidine 75mg/m² days 1-7 Avapritinib orally on days 8-21 (28-day cycle)

Timeline

• Start date: 2025-05-15
• Primary completion: 2027-05-15
• Completion: 2027-12-31
• First posted: 2025-06-19
• Last updated: 2025-06-19

Locations

1 site across 1 country: China