Avapritinib in CBF-AML With KIT Mutations

Core Binding Factor Acute Myeloid Leukemia Clinical Trial

Official title:

Avapritinib in Relapsed Refractory or MRD-positive CBF-AML With KIT Mutations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05821738
• Other study ID #: SZ-AML-KIT
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Suning Chen
• Phone: +8613814881746
• Email: chensuning[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

1. Patients with acute myeloid leukemia accompanied by t(8; 21)/RUNX1-RUNX1T1, or inv(16)/t(16; 16)/CBFß-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.

Related Conditions & MeSH terms

• Core Binding Factor Acute Myeloid Leukemia

Intervention

Drug:
• Avapritinib
administered orally

Locations

Country	Name	City	State
China	First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite complete remission (CRc)	The proportion of participants who achieve Composite complete remission (CRc),which includes complete remission (CR)?CR with partial hematologic recovery (CRh)?CR with incomplete blood count recovery (CRi) and morphology leukemia free (MLFS) based on response criteria for AML.	Assessed at protocol-defined timepoints through end of study, up to approximately 36 months.
Secondary	MRD-negative rate	The proportion of participants who achieve a negative molecular MRD.	Assessed at protocol-defined timepoints through end of study, up to approximately 36 months.
Secondary	Progression-free survival (PFS)	The Kaplan-Meier method will be used to assess PFS probabilities.	From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 1 to 3 years.
Secondary	Overall survival (OS)	The Kaplan-Meier method will be used to assess OS probabilities.	From the first day of treatment to time of death from any cause, assessed up 1 to 3 years.
Secondary	Incidence of adverse events (AEs)	Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients with AEs will be estimated, along with the 95% credible interval.	Up to approximately 1 to 3 years.