Clinical trial NCT06316960: Safety and Efficacy of Avapritinib in Relapsed or Refractory Pediatric CBF-AML With KIT Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: AML, Childhood
Relapse/Recurrence
Refractory AML
Core Binding Factor Acute Myeloid Leukemia
C-KIT Mutation
Keywords: Avapritinib
KIT
CBF AML
Childhood
Relapsed/Refractory
Lead sponsor: Children's Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-03-19
Enrollment: 50
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite remission rate (CRc)
timeFrame: The evaluation time point is day28-day35 from the start of regimen.
Secondary outcomes:
measure: Overall survival
timeFrame: From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.
measure: Progression-free survival
timeFrame: From date of enrollment until the date of disease progression, conﬁrmed relapse, or death, whichever occurred ﬁrst, assessed up to 60 months.
Other outcomes:
Locations:
city: Hefei
country: China
facility: First Affiliated Hospital Of University of Science and Technology of China
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Guangzhou
country: China
facility: Guangzhou Women and Children Medical Center
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Kaifeng
country: China
facility: Kaifeng Children's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: XiangYa Hospital Central South University
state: Hunan
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Children's Hospital
state: Jiangsu
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Children's Hospital Of Fudan University
state: Shanghai
Study officials:
affiliation: Children 's Hospital of Soochow University
name: Shaoyan Hu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: