Avapritinib in CBF-AML With KIT Mutations

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

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.

Study Overview

• Status: Recruiting
• Conditions: Core Binding Factor Acute Myeloid Leukemia; KIT Mutation-Related Tumors
• Intervention / Treatment: Drug: Avapritinib

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Suning Chen; Phone Number: +8613814881746; Email: chensuning@sina.com
• Study Contact Backup: Name: Haiping Dai; Phone Number: 13914086271; Email: daihaiping@126.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • First Affiliated Hospital of Soochow University
      • Contact: Suning Chen, PhD; Phone Number: +8613814881746; Email: chensuning@sina.com
      • Contact: Haiping Dai; Phone Number: 13914086271; Email: daihaiping@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; The treatment group will receive avapritinib orally. The dosage is 100mg to 300mg qd, allowed to combine with other chemotheray drugs.	Drug: Avapritinib; administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 6, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: SZ-AML-KIT

Drug and device information, study documents

• 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