Avapritinib with standard chemotherapy for newly diagnosed KIT‑mutant CBF‑AML
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
This will test whether adding avapritinib to standard induction and consolidation therapies helps adults newly diagnosed with KIT‑mutated core‑binding factor AML achieve deeper remissions and live longer.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 78 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | The First Affiliated Hospital of Soochow University Academic / other |
| Drugs / interventions | dasatinib, gilteritinib, avapritinib, chemotherapy |
| Locations | 1 site (Suzhou, Jiangsu) |
| Trial ID | NCT07028073 on ClinicalTrials.gov |
What this trial studies
This phase I–II trial enrolls adults with newly diagnosed core‑binding factor AML who have KIT mutations and assigns them to a fit arm (avapritinib plus IA: cytarabine + idarubicin) or an unfit arm (avapritinib plus VA: azacitidine + venetoclax). Phase I uses dose escalation to determine the maximum tolerated dose and recommended phase II dose of avapritinib for each combination, and phase II studies efficacy and safety. Treatment includes induction, consolidation, and maintenance phases with sequential administration designed to manage overlapping toxicities. Key endpoints include dose‑limiting toxicities, MRD negativity, complete remission rates, relapse‑free survival, and overall survival.
Who should consider this trial
Good fit: Adults (≥18 years) with newly diagnosed core‑binding factor AML carrying KIT mutations and the specified t(8;21) or inv/t(16) rearrangements are ideal, with fit patients (ECOG 0–1, often <65) placed in the IA arm and older or comorbid patients in the VA arm.
Not a fit: Patients without KIT mutations or the specified CBF rearrangements, those previously treated beyond minimal cytoreduction, or those with contraindications to the study drugs are unlikely to benefit from this regimen.
Why it matters
Potential benefit: If successful, the combination could raise rates of deep remission (MRD negativity) and lower relapse risk in KIT‑mutated CBF‑AML, potentially improving long‑term survival.
How similar studies have performed: Previous attempts to target KIT in AML have shown mixed results and avapritinib has not been widely tested in KIT‑mutant CBF‑AML, so this specific combination is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * 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
Where this trial is running
Suzhou, Jiangsu
- The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
Study contacts
- Study coordinator: Su-ning Chen, M.D.
- Email: chensuning@sina.com
- Phone: 008613814881746
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.