Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study

摘要: Summary Background Outcomes for children with relapsed or refractory acute myeloid leukaemia remain poor. The BCL-2 inhibitor, venetoclax, has shown promising activity in combination hypomethylating agents and low-dose cytarabine older adults whom chemotherapy is not suitable newly diagnosed leukaemia. We aimed to determine the safety explore of venetoclax standard high-dose paediatric patients Methods did a phase 1, dose-escalation study at three research hospitals USA. Eligible were aged 2–22 years ambiguous lineage adequate organ function performance status. During dose escalation, participants received orally once per day continuous 28-day cycles either 240 mg/m2 360 mg/m2, intravenously every 12 h 100 20 doses 1000 eight doses, without intravenous idarubicin (12 mg/m2) as single dose, using rolling-6 accrual strategy. primary endpoint was recommended 2 plus secondary proportion treated who achieved complete remission incomplete haematological recovery. Analyses done on therapy. registered ClinicalTrials.gov ( NCT03194932 ) now enrolling address exploratory objectives. Findings Between July 2017, 2, 2019, 38 enrolled (aged 3–22 years; median 10 [IQR 7–13]), 36 therapy follow-up 7·1 months (IQR 5·1–11·2). found be (maximum 600 mg) combined (1000 doses), dose). Overall responses observed 24 (69%) 35 evaluable after cycle 1. Among 14 (70%, 95% CI 46–88) showed response recovery, two (10%) partial response. most common grade 3–4 adverse events febrile neutropenia (22 [66%]), bloodstream infections (six [16%]), invasive fungal [16%]). Treatment-related death occurred one patient due colitis sepsis. Interpretation heavily suggests that this should tested high-risk Funding US National Institutes Health, American Lebanese Syrian Associated Charities, AbbVie, Gateway Cancer Research.