Clinical trial NCT06765915: Avapritinib Maintenance for AML With KIT Mutations
Official title: Avapritinib Maintenance Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia With KIT Mutations
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: AML, Adult
Keywords: AML
KIT mutation
avapritinib
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2025-01-09
Enrollment: 47
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative incidence of relapse
timeFrame: through study completion, an average of 2 year
Secondary outcomes:
measure: Overall survival
timeFrame: through study completion, an average of 2 year
measure: Non relapse mortality
timeFrame: through study completion, an average of 2 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital of Shanghai Jiaotong University
state: Shanghai
Study officials:
References: