Overview
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.
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:
- 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.
- 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.
Eligibility
Inclusion Criteria:
- 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.
- Bone marrow molecular biology detected C-KIT D816 or C-KIT N822 mutations
- Patients with CBFB::MYH11 gene or RUNX1::RUNX1T1 fusion gene detected.
- Eastern Cancer Collaboration Group (ECOG) physical status score 0-2 points.
- 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)
- Volunteer to participate in clinical studies and sign informed consent, willing to follow and able to complete all trial procedures.
Exclusion Criteria:
- Known allergy to KIT inhibitor drug analogues.
- Patients who have received previous treatment with Midostaurin.
- Patients who have previously been treated with mutation-specific C-KIT inhibitors and have developed disease progression during treatment.
- FLT3-ITD mutation in patients with recurrent/refractory disease (except low gene ratio).
- HIV infected persons, HBV, HCV active infected persons.
- Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases and other diseases.
- With uncontrolled active GVHD (NIH for GVHD diagnosis and classification standards, aGVHD classification refer to the improved Glucksberg standard).
- Central nervous system leukemia.