Phase 1 Trial of Venetoclax with Cladribine, Cytarabine, G-CSF, and Mitoxantrone for AML and High-Grade Myeloid Neoplasm

• MTD was venetoclax 400 mg d1-14, cladribine 5 mg/m² d1-5, cytarabine 1.5 g/m² d1-5, and mitoxantrone 16 or 18 mg/m² d1-3

• 65% (13/20, 95% confidence interval 41-85%) patients achieved CR or CRi and 28-day mortality was 5%

Intensifying induction by combining venetoclax with a high-dose cytarabine regimen may improve outcomes for high-risk populations such as adult patients with adverse-risk newly diagnosed or relapsed acute myeloid leukemia. In a phase 1 trial testing the novel combination of venetoclax and CLAG-M, the maximum tolerated dose (MTD) was venetoclax 400 mg days 1-14, combined with cladribine 5 mg/m² days (d) 1-5, cytarabine 1.5 g/m² days 1-5, G-CSF 5 mcg/kg days 0-5, and mitoxantrone 16 or 18 mg/m² days 1-3 (for relapsed/refractory and newly diagnosed adverse-risk patients respectively). 28-day mortality was 5%. Composite complete remission rate (CR + CRi) was 65%. These findings support further phase 2 study of venetoclax in combination with CLAG-M. Clinical Trial ID: NCT04797767.