Avapritinib Maintenance for AML With KIT Mutations

Phase 2

Not yet recruiting

• Conditions: AML, Adult
• Interventions: Drug: Avapritinib

• Registration Number: NCT06765915
• Lead Sponsor: Ruijin Hospital

Brief Summary

A multicenter, single-arm clinical study of evaluate the efficacy and safety of avapritinib as maintenance therapy following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with KIT mutation.

Detailed Description

It has been reported that in patients with CBF-associated acute myeloid leukemia (CBF-AML), c-kit mutations occur preferentially in patients with core-binding factor ((8; 21) and inv(16) or t(16; 16) (referred to as inv(16)) rearrangements. However, c-KIT gene mutations, which occur more frequently in patients with CBF-AML, have an incidence of 10% to 45%, which in turn leads to relapse, suggesting a poor prognosis. Nearly 50% of AML patients with concomitant t(8;21) have the c-KIT-D816 mutation. Among AML patients with t(8; 21), patients with c-KIT D816 mutation had significantly shorter OS and EFS than those without this mutation.

Avapritinib, is a novel inhibitor of KIT and PDGFRA-activating ring mutants and a potent and selective inhibitor of KIT D816V, and preclinical studies have demonstrated that compared to Midostauin, Avapritinib is 10-fold more potent against this mutant kinase was 10-fold more potent. A retrospective study \[ 14 \] analyzed the efficacy of Avapritinib in patients with t (8;21) AML with KIT mutations who failed allo-HSCT treatment. Among the 13 patients in the D816 mutation, 8 cases reduced RUNX1-RUNX1T1 transcript levels by ≥1 log after 1 month of treatment, and 3 cases turned negative. However, whether avapritinib is effective for maintenance therapy in CBF-AML patients who harbor KIT mutations is unknown.

There is a lack of prospective, controlled studies to clarify the efficacy and safety of XPO1 inhibitor combined with venetoclax as maintenance therapy after allo-HSCTin patients with intermediate- to high-risk AML/MDS, especially those with out specific gene mutation which would be targeted with commerically available inhibitors. Therefore, this multicenter, single-arm study is designed to assess the efficacy and safety of avapritinib as maintenance therapy in CBF-AML patients who harbor KIT mutations after allo-HSCT, with the aim of providing a reference for clinical treatment.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-05
• Study First Submitted QC: 2025-01-05
• Last Update Submitted: 2025-01-05
• Study First Posted: 2025-01-09
• Last Update Posted: 2025-01-09
• Study Start: 2025-02-01
• Primary Completion: 2026-02-01
• Study Completion: 2028-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

• Age≥ 14 years old;
• First allo-HSCT for AML (including secondary AML) ;
• KIT mutation at diagnosis (no restriction on locus for kit mutation
• CR and negative MFC-MRD prior to initiation of maintenance therapy;
• Absolute neutrophil count ≥ 1.0 x 109 /L, platelets ≥ 75 x 109 /L, hemoglobin ≥ 80 g/L before maintenance;
• Normal functioning of major organs and laboratory findings in accordance with the following criteria:AST and ALT) ≤ 3x ULN; Total serum bilirubin ≤ 1.5x ULN unless the patient has Gilbert syndrome; patients with Gilbert-Meulengracht syndrome with bilirubin ≤ 3.0 times the upper limit of normal and direct bilirubin ≤ 1.5 times the upper limit of normal may be included; HB ≥ 70 g/L (had not received a red blood cell transfusion within 1 week prior to administration); ANC ≥ 0.8 x 10^9/L (had not received long-acting colony-stimulating factor (LACSF) within 1 week prior to administration and short-acting colony-stimulating factor (SACSF) within 3 days prior to administration); Platelet count ≥ 20 x 10^9/L (had not received a platelet transfusion within 1 week prior to administration); serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 60 mL/min; Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN, Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; Left ventricular ejection fraction (LVEF) ≥45%;
• ECOG PS 0-2 points;
• Expected survival ≥ 3 months;
• Patient consent

Exclusion Criteria

• concurrently receiving other targeted therapies for AML;
• Prior treatment with a TKI inhibitor that proved ineffective;
• with concurrent FLT3-ITD mutations at enrollment;
• Acute/chronic graft-versus-host disease requiring systemic immunosuppressive therapy prior to maintenance therapy;
• Accompanied by other malignant tumors requiring treatment;
• Have important organ-based diseases: e.g., myocardial infarction, chronic cardiac insufficiency, decompensated hepatic insufficiency, renal failure;
• Active, uncontrolled infection;
• HIV-positive, active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy;
• Other interventional clinical studies have been enrolled;
• Men and women of childbearing potential are unwilling to use contraception during and for 12 months after treatment;
• The investigator believes that there are other conditions that make the patient unsuitable for participation in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental arm	Avapritinib	Allo-HSCT recipients will begin maintenance therapy with oral Avapritinib tablets at a dose of 100 mg/day, starting 2-4 months post-transplantation. Each treatment cycle lasts 28 days, and therapy will continue for up to 2 years or until disease progression or unacceptable toxicity occurs.

Primary Outcome Measures

Name	Time	Method
Cumulative incidence of relapse	through study completion, an average of 2 year	disease relapse

Secondary Outcome Measures

Name	Time	Method
Overall survival	through study completion, an average of 2 year	death as a result of any causes
Non relapse mortality	through study completion, an average of 2 year	death without disease progression or relapse

Trial Locations

Locations (1)

Ruijin Hospital of Shanghai Jiaotong University; 🇨🇳 Shanghai, Shanghai, China