Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed AML After Allo-HSCT

An Exploratory Clinical Study of the Safety and Efficacy of Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

This is a single-center, prospective, single-arm, exploratory clinical study. To explore the efficacy and safety of avapritinib in patients with recurrent acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation with C-KIT mutation RUNX1::RUNX1T1 or CBFB::MYH11.

Study Overview

• Status: Recruiting
• Conditions: AML (Acute Myelogenous Leukemia)
• Intervention / Treatment: Drug: Avapritinib, azacitidine, Venetoclax

Detailed Description

We enrolled 20 patients with recurrent acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation of RUNX1::RUNX1T1 or CBFB::MYH11 with C-KIT mutation.

The study was divided into induction therapy period and consolidation therapy period, and the study design was as follows:

A: Induction therapy period: After patients were screened and enrolled, they began to receive 1-2 cycles of induction therapy, and the specific administration regimen was as follows: Avapritinib 100mg po qd D1-D14, azacitidine 35mg/m2 ih D1-D5, Venetoclax 100mg po qd D1-D14. The 28-day cycle was followed by curative effect evaluation at the end of each cycle. Patients who achieved complete remission entered the consolidation treatment stage.

B: Consolidation therapy period: Patients who achieved complete remission after 1-2 cycles of induction therapy continued to receive avapritinib 100mg/d po. monotherapy for consolidation therapy, with a cycle of 28 days and a total of 4 cycles.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Erlie Jiang; Phone Number: 15122538107; Email: jiangerlie@ihcams.ac.cn
• Study Contact Backup: Name: Yigeng Cao; Phone Number: 18622477067; Email: caoyigeng@ams.ac.cn

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital
    • Contact: Erlie Jiang; Phone Number: +86-15122538106; Email: jiangerlie@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects met the criteria for recurrence after allogeneic transplantation: re-emergence of leukemia cells or bone marrow original cells in peripheral blood >5% (except for other causes such as bone marrow recovery period) or extramedullary leukemia cell infiltration or molecular or cytogenetic recurrence.
2. Bone marrow molecular biology detected C-KIT D816 or C-KIT N822 mutations
3. Patients with CBFB::MYH11 gene or RUNX1::RUNX1T1 fusion gene detected.
4. Eastern Cancer Collaboration Group (ECOG) physical status score 0-2 points.
5. Liver, kidney and cardiopulmonary functions met the following requirements: Within 2 weeks before enrollment ① creatinine ≤1.5 upper limit of normal value; ② Left ventricular ejection fraction ≥50%; ③ Blood oxygen saturation >91%; ④ Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; Myocardial enzymes < 2 times the upper limit of normal (for the same age)
6. Volunteer to participate in clinical studies and sign informed consent, willing to follow and able to complete all trial procedures.

Exclusion Criteria:

1. Known allergy to KIT inhibitor drug analogues.
2. Patients who have received previous treatment with Midostaurin.
3. Patients who have previously been treated with mutation-specific C-KIT inhibitors and have developed disease progression during treatment.
4. FLT3-ITD mutation in patients with recurrent/refractory disease (except low gene ratio).
5. HIV infected persons, HBV, HCV active infected persons.
6. Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases and other diseases.
7. With uncontrolled active GVHD (NIH for GVHD diagnosis and classification standards, aGVHD classification refer to the improved Glucksberg standard).
8. Central nervous system leukemia.

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: Arm 1; Avapritinib combined with Azacitidine and Venetoclax

Drug: Avapritinib, azacitidine, Venetoclax; A: Induction therapy period: After patients were screened and enrolled, they began to receive 1-2 cycles of induction therapy, and the specific administration regimen was as follows: Avapritinib 100mg po qd D1-D14, azacitidine 35mg/m2 ih D1-D5, Venetoclax 100mg po qd D1-D14. The 28-day cycle was followed by curative effect evaluation at the end of each cycle. Patients who achieved complete remission entered the consolidation treatment stage. B: Consolidation therapy period: Patients who achieved complete remission after 1-2 cycles of induction therapy continued to receive avapritinib 100mg/d po. monotherapy for consolidation therapy, with a cycle of 28 days and a total of 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-month ORR after induction therapy	2-month objective remission rate after induction therapy	2 months after induction therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate after induction therapy	CR rate after 2 months	2 months after induction therapy
MRD negative rate after induction therapy	MRD negative rate after 2 months	2 months after induction therapy
Response rate after Consolidation treatment	Response rate after 6 months	6 months after Consolidation treatment
Safety	Types of adverse events (AE), AE severity, Relevance to study drugs	2 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Erlie Jiang, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): January 20, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Venetoclax; Azacitidine
• Other Study ID Numbers: IIT2024097

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