Although the survival rates for children with acute myeloid leukemia (AML) have reached 70%, little improvement has been made in the past 20 years. Approximately 25% of patients relapse and only about 40% of these patients are subsequently cured. It is highly unlikely that improvements can be made simply by modifying the doses or schedules of conventional agents; instead, the incorporation of novel agents into treatment regimens is urgently needed. The Gateway-funded VENAML trial was the first clinical trial of venetoclax in pediatric patients and the first trial of venetoclax combined with intensive chemotherapy in any patient population. Venetoclax targets and inhibits a family of proteins called BCL2. When there is high amount of BCL2, it prevents cancer cells from being killed by immune cells as they inhibit a process called apoptosis (or programmed cell death) and this is associated with resistance to chemotherapy and worsened clinical outcomes. The results of this phase I trial demonstrated that the combination of venetoclax plus high-dose cytarabine, with or without idarubicin, could be safely administered to children and adolescents with relapsed or refractory AML. Among the 20 patients treated at the recommended phase 2 dose, 14 (70%) achieved a complete response, an encouraging response rate in this heavily treated population. This phase II study will therefore assess the proportion of newly diagnosed AML patients who become minimal residual disease negative after treatment with venetoclax in combination with standard chemotherapy. This will be the first clinical trial that incorporates venetoclax into the treatment regimen for pediatric patients with newly diagnosed AML.
Trial Registration: ClinicalTrials.gov Identifier: Pending