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
The First Affiliated Hospital of Soochow University
78 participants
May 15, 2025
INTERVENTIONAL
Conditions
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?
Eligibility
Inclusion Criteria6
- Age ≥18 years, both genders
- Diagnosis of acute myeloid leukemia according to WHO 2022 criteria
- Treatment-naive patients (hydroxyurea or low-dose cytarabine \<0.5g cumulative dose allowed)
- Bone marrow detection of KIT mutations with concurrent t(8;21)(q22;q22.1) or RUNX1::RUNX1T1 fusion gene; or inv(16)(p13.1q22) or t(16;16)(p13.1;q22) or CBFβ::MYH11 fusion gene
- Life expectancy \>12 weeks Group A: ≥18 and \<65 years with ECOG 0-1; Group B: ≥65 years or ≥18 and \<65 years with comorbidities (ECOG ≥2, cardiac disease, creatinine clearance 30-50ml/min, or mild hepatic impairment)
- Adequate organ function: bilirubin ≤2×ULN, ALT/AST ≤3×ULN (≤5×ULN if leukemic infiltration), creatinine clearance ≥30ml/min, left ventricular ejection fraction \>45%
Exclusion Criteria6
- Known hypersensitivity to KIT inhibitors, cytarabine, idarubicin, venetoclax, azacitidine or similar agents
- Concurrent use of other KIT inhibitors (dasatinib, sorafenib, gilteritinib, midostaurin)
- Intracranial hemorrhage on imaging or unresolved prior intracranial bleeding
- Active uncontrolled infection
- Significant organ dysfunction: myocardial infarction, chronic heart failure, decompensated liver dysfunction, renal failure
- Pregnancy or breastfeeding
Interventions
Cytarabine 100mg/m² days 1-7 Idarubicin 12mg/m² days 1-3 Avapritinib orally on days 8-21 (28-day cycle)
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)
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07028073