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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-01

Study Completion Date

2027-03-31

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Relapsed/Refractory CBF-AML with KIT mutation

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.

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.

Azacitidine Injection

Intervention Type DRUG

75mg/m2/d for weighing \>10kg, 2.5mg/kg/d for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.

Decitabine Injection

Intervention Type DRUG

20mg/m2/d for weighing \>10kg, 0.67mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.

Idarubicin Hydrochloride

Intervention Type DRUG

5mg/m2/day for weighing \>10kg, 0.17mg/kg/day for weighing ≤ 10kg, d 6, 8, 10 (d 8, 10, 12 for azacitidine) ivgtt, qod, more than 1 hour at 10 am.

Cytarabine

Intervention Type DRUG

10mg/m2/day for weighing \>10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.

Granulocyte Colony-Stimulating Factor

Intervention Type DRUG

300ug/day for weighing \>10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.

Interventions

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Avapritinib

50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.

Intervention Type DRUG

Azacitidine Injection

75mg/m2/d for weighing \>10kg, 2.5mg/kg/d for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.

Intervention Type DRUG

Decitabine Injection

20mg/m2/d for weighing \>10kg, 0.67mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.

Intervention Type DRUG

Idarubicin Hydrochloride

5mg/m2/day for weighing \>10kg, 0.17mg/kg/day for weighing ≤ 10kg, d 6, 8, 10 (d 8, 10, 12 for azacitidine) ivgtt, qod, more than 1 hour at 10 am.

Intervention Type DRUG

Cytarabine

10mg/m2/day for weighing \>10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.

Intervention Type DRUG

Granulocyte Colony-Stimulating Factor

300ug/day for weighing \>10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.

Intervention Type DRUG

Other Intervention Names

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AYVAKIT Azacitidine Decitabine Idarubicine CYTOSAR Recombinant Human Granulocyte Colony-Stimulating Factor Injection

Eligibility Criteria

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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.

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Shaoyan Hu

Study Chair

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shaoyan Hu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children 's Hospital of Soochow University

Locations

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