Safety and Efficacy of Avapritinib in Relapsed or Refractory Pediatric CBF-AML With KIT Mutation

March 12, 2024 updated by: Shaoyan Hu, Children's Hospital of Soochow University

A Prospective, Multicenter Clinical Study on The Safety and Efficacy of Avapritinib in The Treatment of Relapsed/Refractory Pediatric Core Binding Factor Acute Myeloid Leukemia (CBF-AML) With KIT Mutation

The purpose of this study is to evaluate the efficacy and safety of avapritinib in relapsed or refractory pediatric core binding factor acute myeloid leukemia with KIT mutation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, single-arm, prospective, and intervention trial. About 30% of core binding factor acute myeloid leukemia (CBF-AML) patients still relapse under current treatment. Some studies have found that KIT mutations, especially the D816V mutation, may predict relapse and decrease overall survival (OS) in CBF-AML. Avapritinib has been approved for the treatment of gastrointestinal stromal tumors with KIT or PDGFRA mutations. Avapritinib was also effective for the treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and KIT mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation in a single-center, retrospective report. 11 centers from China carry out the AVACBFKIT regimen including Avapritinib, hypomethylating agents and low dose chemotherapy for the treatment of relapsed or refractory pediatric CBF-AML with KIT mutation. The main focus of this study is to evaluate the efficacy and safety of avapritinib in the regimen.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Shaoyan Hu, MD, PhD
  • Phone Number: +86-13771870462
  • Email: hsy139@126.com

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230000
        • Not yet recruiting
        • The Second Hospital of Anhui Medical University
        • Contact:
          • Ninglin Wang, MD
          • Phone Number: +86-13721113063
          • Email: zwnltt@126.com
      • Hefei, Anhui, China, 230000
        • Not yet recruiting
        • First Affiliated Hospital of University of Science and Technology of China
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Not yet recruiting
        • Guangzhou Women and Children Medical Center
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Not yet recruiting
        • The First Affiliated Hospital of Guangxi Medical University
        • Contact:
    • Henan
      • Kaifeng, Henan, China, 475000
        • Not yet recruiting
        • Kaifeng Children's Hospital
        • Contact:
      • Zhengzhou, Henan, China, 450052
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410008
        • Not yet recruiting
        • Xiangya Hospital Central South University
        • Contact:
      • Changsha, Hunan, China, 410000
        • Not yet recruiting
        • Third Xiangya Hospital of Central South University
        • Contact:
    • Jiangsu
      • Suzhou, Jiangsu, China, 215000
        • Recruiting
        • Children's Hospital of Soochow University
        • Contact:
        • Sub-Investigator:
          • Jie Li, MD
        • Sub-Investigator:
          • Li Gao, MD
        • Contact:
          • Shaoyan Hu, MD, PhD
          • Phone Number: +86-13771835430
          • Email: hsy139@126.com
        • Principal Investigator:
          • Shaoyan Hu, MD, PhD
        • Principal Investigator:
          • Peifang Xiao, MD
        • Sub-Investigator:
          • Jun Lu, MD
      • Xuzhou, Jiangsu, China, 221000
        • Not yet recruiting
        • Xuzhou Children's Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250000
        • Not yet recruiting
        • Qilu Hospital of Shandong University
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Not yet recruiting
        • Children's Hospital of Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Gender unlimited;
  2. Under 18 years;
  3. Diagnosis of acute myeloid leukemia (according to the 2022 WHO classification).
  4. Presence of t(8;21)/RUNX1::RUNX1T1 or inv(16)/t(16;16)/CBFβ::MYH11;
  5. KIT mutation;
  6. Refractory AML: AML patients who do not achieve CR or CRi after induction therapy;
  7. Relapsed AML: patients who achieved remission after consolidation therapy or transplantation, FISH confirmed that the fusion gene turned positive, or extramedullary leukemia infiltration;
  8. No active infections;
  9. Liver function: Tbil ≤2×ULN, ALT/AST ≤3×ULN, creatinine clearance ≥50ml/min;
  10. ECOG score <2;
  11. Expected survival time >12 weeks;
  12. Participants must have the ability to understand and be willing to participate in this study and must sign an informed consent form.

Exclusion Criteria:

  1. Have received prior treatment with avapritinib;
  2. Receiving other targeted therapies for AML at the same time, such as dasatinib, sorafenib, gilteritinib, venetoclax, etc;
  3. Presence of active uncontrolled infection (including bacterial, fungal, or viral infection);
  4. Present of significant underlying organ diseases: such as myocardial infarction, chronic heart failure, decompensated liver or kidney dysfunction；
  5. With other malignancies requiring treatment；
  6. Already enrolled in another interventional clinical study；
  7. The researchers determined that the individual is not suitable to participate in this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Relapsed/Refractory CBF-AML with KIT mutation
The relapsed/refractory patients will receive a combination treatment of decitabine/azacitidine+ IdAG (idarubicine + cytarabine + granulocyte stimulating factor)regimen along with avapritinib. CBF-AML with KIT mutated patients with molecular relapse after hematopoietic stem cell transplantation may receive avapritinib combined with demethylating agents or interferon or donor lymphocyte infusion without low-dose chemotherapy. The dose of avapritinib will start at 50mg/m2/d, and if platelets stabilize at 50 ×10^9/L and neutrophils stabilize above 1.0 ×10^9/L after one week, the dose can be increased to 100mg/m2/d, with a maximum daily dose of 100mg. Avapritinib should be discontinued in the presence of febrile neutropenia or active infection, and avapritinib can be resumed once the infection is controlled, with each treatment cycle not exceeding 28 days.
Drug: Avapritinib
50mg/m2/day for weighing bodyweight >10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.
Other Names:
  • AYVAKIT
Drug: Azacitidine Injection
75mg/m2/d for weighing >10kg, 2.5mg/kg/d for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.
Other Names:
  • Azacitidine
Drug: Decitabine Injection
20mg/m2/d for weighing >10kg, 0.67mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.
Other Names:
  • Decitabine
Drug: Idarubicin Hydrochloride
5mg/m2/day for weighing >10kg, 0.17mg/kg/day for weighing ≤ 10kg, d 6, 8, 10 (d 8, 10, 12 for azacitidine) ivgtt, qod, more than 1 hour at 10 am.
Other Names:
  • Idarubicine
Drug: Cytarabine
10mg/m2/day for weighing >10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.
Other Names:
  • CYTOSAR
Drug: Granulocyte Colony-Stimulating Factor
300ug/day for weighing >10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.
Other Names:
  • Recombinant Human Granulocyte Colony-Stimulating Factor Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite remission rate (CRc)
Time Frame: The evaluation time point is day28-day35 from the start of regimen.
Composite remission rate (CRc), including the sum of the number of patients with complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete blood count recovery (CRi), and morphologically leukemia-free (MLFS) as a percentage of the total number of patients who participated in the efficacy analysis.
The evaluation time point is day28-day35 from the start of regimen.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.
Overall survival (OS) was defined as the date from enrollment to the date of death or last follow-up for surviving patients.
From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.
Progression-free survival
Time Frame: From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 months.
Progression-free survival (PFS) was defined as the date from enrollment to the date of disease progression, confirmed relapse, or death, whichever occurred first.
From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Soochow University

Investigators

  • Principal Investigator: Shaoyan Hu, MD, PhD, Children 's Hospital of Soochow University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

March 12, 2024

First Submitted That Met QC Criteria

March 12, 2024

First Posted (Actual)

March 19, 2024

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVACBFKIT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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