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

Официальное название

A Prospective, Multicenter Clinical Study on The Safety and Efficacy of Avapritinib in The Treatment of Relapsed/Refractory Pediatric Core Binding Factor Acute Myeloid Leukemia (CBF-AML) With KIT Mutation

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Avapritinib
  50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.
• Препарат 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.
• Препарат 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.
• Препарат 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.
• Препарат Cytarabine
  10mg/m2/day for weighing \>10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.
• Препарат Granulocyte Colony-Stimulating Factor
  300ug/day for weighing \>10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.

Первичные конечные точки

• Composite remission rate (CRc) [Срок оценки: The evaluation time point is day28-day35 from the start of regimen.]

Вторичные конечные точки (2)

• Overall survival [Срок оценки: From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.]
• Progression-free survival [Срок оценки: From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 months.]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 12 центров

• First Affiliated Hospital Of University of Science and Technology of China — Хэфэй
• The Second Hospital of Anhui Medical University — Хэфэй
• Guangzhou Women and Children Medical Center — Гуанчжоу
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• Kaifeng Children's Hospital — Kaifeng
• The First Affiliated Hospital of Zhengzhou University — Чжэнчжоу
• Third Xiangya Hospital of Central South University — Чанша
• XiangYa Hospital Central South University — Чанша
• … и ещё 4 центра

Идентификаторы

NCT: NCT06316960 · AVACBFKIT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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