Combining avapritinib, azacitidine, and venetoclax for treating relapsed AML after stem cell transplant

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 study is testing a new combination of three medications to see if they can help people with relapsed acute myeloid leukemia feel better after a stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: avapritinib
• Locations: 1 site (Tianjin)
• Trial ID: NCT06783790 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of avapritinib in combination with azacitidine and venetoclax for patients with recurrent acute myeloid leukemia (AML) following allogeneic hematopoietic stem cell transplantation. The study involves a single-center, prospective, single-arm design enrolling 20 patients with specific genetic mutations. Participants undergo an induction therapy period followed by a consolidation therapy period if they achieve complete remission. The treatment regimen includes avapritinib, azacitidine, and venetoclax over a series of 28-day cycles.

Who should consider this trial

Good fit: Ideal candidates are patients with recurrent AML after allogeneic transplantation who have specific C-KIT mutations and fusion genes.

Not a fit: Patients without the required genetic mutations or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed AML after stem cell transplantation.

How similar studies have performed: While this approach is exploratory, similar combinations have shown promise in other studies, indicating potential for success.

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.

Where this trial is running

Tianjin

• Institute of Hematology & Blood Diseases Hospital — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Erlie Jiang — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Erlie Jiang

Conditions AML