A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia

NCT07028073 | Recruiting Phase 1

• 1 other identifier: SZ-AML03
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if avapritinib combined with standard induction therapy works to treat newly diagnosed adult acute myeloid leukemia (AML) patients with KIT mutations and t(8;21)(q22;q22.1); inv(16)(p13.1q22) or t(16;16)(p13.1;q22). It will also investigate the safety and tolerability of this combination therapy. The main questions it aims to answer are: To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of avapritinib combined with chemotherapy by Dose-limiting toxicity (DLT). Does this combination therapy improve the rates of minimal residual disease (MRD) negativity and long-term survival outcomes?

Conditions

Acute Myeloid Leukemia With T(8;21)(Q22;Q22); Acute Myeloid Leukemia With T(16;16)(P13;Q22); KIT Gene Mutation; Avapritinib

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended phase 2 dose (RP2D)

  Recommended phase 2 dose (RP2D) of IA-based and VA-based combination with avapritinib schedules

  Approximately 6 months after first patient first visit (FPFV)

• Phase II: MRD (Measure residual disease) negativity rate

  MRD negativity rate - proportion of patients achieving ≥3-log reduction in RUNX1::RUNX1T1 or CBFβ::MYH11 fusion gene levels by qPCR between the 1st and 2nd consolidation courses.

  Aproximatey 2 years after FPFV

Secondary Outcomes (3)

• Overall survival (OS)

  Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.

• Composite complete remission rate (CRc)

  Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.

• Adverse Event

  Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.

Study Arms (2)

Group A (FIT): Avapritinib Combined Intensive Chemotherapy in patients with newly diagnosed AML

EXPERIMENTAL

Drug: Group A (FIT): Avapritinib + IA regimen

Group B (UNFIT): Avapritinib Combined Venetoclax/Azacitidine in patients with newly diagnosed AML

EXPERIMENTAL

Drug: Group B (UNFIT): Avapritinib + VA regimen

Interventions

Group A (FIT): Avapritinib + IA regimen DRUG

Cytarabine 100mg/m² days 1-7 Idarubicin 12mg/m² days 1-3 Avapritinib orally on days 8-21 (28-day cycle)

Also known as: Group A (Intensive chemotherapy)

Group A (FIT): Avapritinib Combined Intensive Chemotherapy in patients with newly diagnosed AML

Group B (UNFIT): Avapritinib + VA regimen DRUG

Venetoclax 100mg day 1, 200mg day 2, 400mg days 3-28 Azacitidine 75mg/m² days 1-7 Avapritinib orally on days 8-21 (28-day cycle)

Also known as: Group B (Non-intensive chemotherapy)

Group B (UNFIT): Avapritinib Combined Venetoclax/Azacitidine in patients with newly diagnosed AML

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, both genders
• Diagnosis of acute myeloid leukemia according to WHO 2022 criteria
• Treatment-naive patients (hydroxyurea or low-dose cytarabine \<0.5g cumulative dose allowed)
• Bone marrow detection of KIT mutations with concurrent t(8;21)(q22;q22.1) or RUNX1::RUNX1T1 fusion gene; or inv(16)(p13.1q22) or t(16;16)(p13.1;q22) or CBFβ::MYH11 fusion gene
• Life expectancy \>12 weeks Group A: ≥18 and \<65 years with ECOG 0-1; Group B: ≥65 years or ≥18 and \<65 years with comorbidities (ECOG ≥2, cardiac disease, creatinine clearance 30-50ml/min, or mild hepatic impairment)
• Adequate organ function: bilirubin ≤2×ULN, ALT/AST ≤3×ULN (≤5×ULN if leukemic infiltration), creatinine clearance ≥30ml/min, left ventricular ejection fraction \>45%

You may not qualify if:

• Known hypersensitivity to KIT inhibitors, cytarabine, idarubicin, venetoclax, azacitidine or similar agents
• Concurrent use of other KIT inhibitors (dasatinib, sorafenib, gilteritinib, midostaurin)
• Intracranial hemorrhage on imaging or unresolved prior intracranial bleeding
• Active uncontrolled infection
• Significant organ dysfunction: myocardial infarction, chronic heart failure, decompensated liver dysfunction, renal failure
• Pregnancy or breastfeeding

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Central Study Contacts

Su-ning Chen, M.D.

CONTACT

008613814881746; chensuning@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Phase 1: Study treatment will start at level 1, and the therapeutic level will be escalated or descalated depending on the appearance of DLT. DLT will be monitored during cycle 1. Phase I will consist of two parallel dose escalation cohorts, with consecutive assignment to each group. For the dose escalation, we will use two parallel groups following a standard "3+3" design. Patients will be assigned sequentially to each group: Group A receives avapritinib with the IA regimen for fit patients, and Group B receives the VA regimen for those unfit. Phase II includes two treatment arm groups (IA-based RP2D vs. VA-based RP2D). Patients will be enrolled at diagnosis, within a maximum 28-day screening period, and will be assessed for eligibility for intensive therapy and therefore assigned to a treatment arm. All screening activities will be performed after the patient's informed consent form is signed.

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: June 19, 2025
• Study Start: May 15, 2025
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-06

Locations

CN (1)