Clinical trial NCT05821738: Avapritinib in CBF-AML With KIT Mutations
Official title: Avapritinib in Relapsed Refractory or MRD-positive CBF-AML With KIT Mutations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Core Binding Factor Acute Myeloid Leukemia
KIT Mutation-Related Tumors
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2023-04-20
Enrollment: 50
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: AML with t(8; 21)(q22; q22) or inv(16)(p13; q22)/t(16; 16)(p13; q22) is known as CBF-AML. KIT mutations are common in CBF-AML, which have a worse prognosis.This study is aimed to evaluate the efficacy of Avapritinib, an highly specific inhibitor of the KIT gene, in CBF-AML with KIT mutations.

Detailed description: Acute Myeloid Leukemia (AML) with the chromosomal abnormality of t(8; 21)(q22; q22) or inv(16)(p13; q22)/t(16; 16)(p13; q22) is known as the Core Binding Factor AML (CBF-AML). KIT mutation is a common mutation in CBF-AML, which is more likely to relapse and have a worse prognosis.

Avapritinib is an oral tyrosine kinase inhibitor (TKI) with selective inhibitory activity against KIT and PDGFRA. Avapritinib has been approved by FDA for the treatment of gastrointestinal stromal tumors(GIST) with PDGFRA mutations and Advanced systemic mastocytosis (AdvSM). However, the efficacy of avapritinib in AML with KIT mutations is uncertain.

This prospective, multicenter clinical study of the efficacy and safety of avapritinib in relapsed refractory or molecular minimal residual disease (MRD)-positive AML with KIT mutations.

Eligibility criteria: Inclusion Criteria:

1. Patients with acute myeloid leukemia accompanied by t(8; 21)/RUNX1-RUNX1T1, or inv(16)/t(16; 16)/CBFβ-MYH11;
2. Accompanied by KIT mutation
3. Disease recurrence after the first remission, or the mol-MRD remains positive after the morphologic remission of AML.
4. No active infection.
5. Liver function: TBIL≤ 2×ULN,ALT/AST≤ 3×ULN, CCr ≥ 50ml/min，NYHA grading ≤2; SaO2 \>92%.
6. ECOG \<2;

(11) Predicted survival \> 12 weeks.

Exclusion Criteria:

1. Accept other AML targeted therapies, such as dasatinib, sorafenib, gilteritinib, etc. simultaneously;
2. The presence of uncontrolled and active infections (including bacterial, fungal or viral infections).
3. Underlying diseases such as myocardial infarction, chronic heart failure, decompensated liver dysfunction, renal failure, etc.
4. Pregnant or lactating women;
5. Accompanied by other malignant tumors requiring treatment;
6. Other interventional clinical studies have been enrolled.

Primary outcomes:
measure: Composite complete remission (CRc)
timeFrame: Assessed at protocol-defined timepoints through end of study, up to approximately 36 months.
Secondary outcomes:
measure: MRD-negative rate
timeFrame: Assessed at protocol-defined timepoints through end of study, up to approximately 36 months.
measure: Progression-free survival (PFS)
timeFrame: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 1 to 3 years.
measure: Overall survival (OS)
timeFrame: From the first day of treatment to time of death from any cause, assessed up 1 to 3 years.
measure: Incidence of adverse events (AEs)
timeFrame: Up to approximately 1 to 3 years.
Other outcomes:
Locations:
city: Suzhou
country: China
facility: First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: First Affiliated Hospital of Soochow University
name: Suning Chen
role: PRINCIPAL_INVESTIGATOR
References: