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

Launched by INSTITUTE OF HEMATOLOGY & BLOOD DISEASES HOSPITAL, CHINA · Jan 14, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a combination of three medications—avapritinib, azacitidine, and venetoclax—for patients with relapsed acute myeloid leukemia (AML) after receiving a stem cell transplant. The focus is on patients whose leukemia has specific genetic changes called C-KIT mutations or certain gene fusions (RUNX1::RUNX1T1 or CBFB::MYH11). The goal is to see how effective and safe this treatment is for those who have experienced a return of their leukemia after their transplant.

To join the study, participants must have signs of leukemia returning after their transplant, have the specific genetic mutations mentioned, and meet certain health criteria, such as good liver and kidney function. Patients should also be willing to follow the study procedures and provide consent. If eligible, participants can expect close monitoring and care throughout the trial to ensure their safety and to gather valuable information about how well the treatment works. This study is currently recruiting patients aged 65 to 74, and it’s important for potential participants to discuss their options and any questions with their healthcare team.

Gender

ALL

Eligibility criteria

• 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.