Safety and Efficacy of Avapritinib in Relapsed or Refractory Pediatric CBF-AML With KIT Mutation

Children's Hospital of Soochow University

Status and phase: Enrolling; Phase 2

Conditions: AML, Childhood; Refractory AML; C-KIT Mutation; Relapse/Recurrence; Core Binding Factor Acute Myeloid Leukemia

Treatments: Drug: Idarubicin Hydrochloride; Drug: Azacitidine Injection; Drug: Avapritinib; Drug: Granulocyte Colony-Stimulating Factor; Drug: Cytarabine; Drug: Decitabine Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT06316960

AVACBFKIT

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of avapritinib in relapsed or refractory pediatric core binding factor acute myeloid leukemia with KIT mutation.

Full description

This is a multicenter, single-arm, prospective, and intervention trial. About 30% of core binding factor acute myeloid leukemia (CBF-AML) patients still relapse under current treatment. Some studies have found that KIT mutations, especially the D816V mutation, may predict relapse and decrease overall survival (OS) in CBF-AML. Avapritinib has been approved for the treatment of gastrointestinal stromal tumors with KIT or PDGFRA mutations. Avapritinib was also effective for the treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and KIT mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation in a single-center, retrospective report. 11 centers from China carry out the AVACBFKIT regimen including Avapritinib, hypomethylating agents and low dose chemotherapy for the treatment of relapsed or refractory pediatric CBF-AML with KIT mutation. The main focus of this study is to evaluate the efficacy and safety of avapritinib in the regimen.

Enrollment: 50 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Gender unlimited;
2. Under 18 years;
3. Diagnosis of acute myeloid leukemia (according to the 2022 WHO classification).
4. Presence of t(8;21)/RUNX1::RUNX1T1 or inv(16)/t(16;16)/CBFβ::MYH11;
5. KIT mutation;
6. Refractory AML: AML patients who do not achieve CR or CRi after induction therapy;
7. Relapsed AML: patients who achieved remission after consolidation therapy or transplantation, FISH confirmed that the fusion gene turned positive, or extramedullary leukemia infiltration;
8. No active infections;
9. Liver function: Tbil ≤2×ULN, ALT/AST ≤3×ULN, creatinine clearance ≥50ml/min;
10. ECOG score <2;
11. Expected survival time >12 weeks;
12. Participants must have the ability to understand and be willing to participate in this study and must sign an informed consent form.

Exclusion criteria

1. Have received prior treatment with avapritinib;
2. Receiving other targeted therapies for AML at the same time, such as dasatinib, sorafenib, gilteritinib, venetoclax, etc;
3. Presence of active uncontrolled infection (including bacterial, fungal, or viral infection);
4. Present of significant underlying organ diseases: such as myocardial infarction, chronic heart failure, decompensated liver or kidney dysfunction；
5. With other malignancies requiring treatment；
6. Already enrolled in another interventional clinical study；
7. The researchers determined that the individual is not suitable to participate in this trial.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Relapsed/Refractory CBF-AML with KIT mutation

Experimental group

Description:

The relapsed/refractory patients will receive a combination treatment of decitabine/azacitidine+ IdAG (idarubicine + cytarabine + granulocyte stimulating factor)regimen along with avapritinib. CBF-AML with KIT mutated patients with molecular relapse after hematopoietic stem cell transplantation may receive avapritinib combined with demethylating agents or interferon or donor lymphocyte infusion without low-dose chemotherapy. The dose of avapritinib will start at 50mg/m2/d, and if platelets stabilize at 50 ×10\^9/L and neutrophils stabilize above 1.0 ×10\^9/L after one week, the dose can be increased to 100mg/m2/d, with a maximum daily dose of 100mg. Avapritinib should be discontinued in the presence of febrile neutropenia or active infection, and avapritinib can be resumed once the infection is controlled, with each treatment cycle not exceeding 28 days.

Treatment:

Drug: Decitabine Injection

Drug: Cytarabine

Drug: Granulocyte Colony-Stimulating Factor

Drug: Avapritinib

Drug: Azacitidine Injection

Drug: Idarubicin Hydrochloride