Avapritinib in CBF-AML With KIT Mutations

• Sponsor: The First Affiliated Hospital of Soochow University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05821738
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 43
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Core Binding Factor Acute Myeloid Leukemia; KIT Mutation-Related Tumors	Drug: Avapritinib	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Avapritinib in Relapsed Refractory or MRD-positive CBF-AML With KIT Mutations
• Actual Study Start Date: Jun 1, 2022
• Anticipated Primary Completion Date: Dec 31, 2024
• Anticipated Study Completion Date: Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Group	Drug: Avapritinib; administered orally

Outcome Measures

Primary Outcome Measures

1. Composite complete remission (CRc) [Assessed at protocol-defined timepoints through end of study, up to approximately 36 months.]

   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.

Secondary Outcome Measures

1. MRD-negative rate [Assessed at protocol-defined timepoints through end of study, up to approximately 36 months.]

   The proportion of participants who achieve a negative molecular MRD.

2. Progression-free survival (PFS) [From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 1 to 3 years.]

   The Kaplan-Meier method will be used to assess PFS probabilities.

3. Overall survival (OS) [From the first day of treatment to time of death from any cause, assessed up 1 to 3 years.]

   The Kaplan-Meier method will be used to assess OS probabilities.

4. Incidence of adverse events (AEs) [Up to approximately 1 to 3 years.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215000

Sponsors and Collaborators

• The First Affiliated Hospital of Soochow University

Investigators

• Principal Investigator: Suning Chen, First Affiliated Hospital of Soochow University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chen Suning, Principal Investigator, The First Affiliated Hospital of Soochow University
• ClinicalTrials.gov Identifier: NCT05821738
• Other Study ID Numbers: SZ-AML-KIT
• First Posted: Apr 20, 2023
• Last Update Posted: Apr 20, 2023
• Last Verified: Apr 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Study Results

No Results Posted as of Apr 20, 2023