Venetoclax in combination with cytarabine with or without idarubicin or azacitidine in children, adolescents, and young adults with relapsed or refractory acute myeloid leukaemia (VENAML): a multicentre, phase 1 expansion study
Abstract
Background: The prognosis for paediatric patients with relapsed or refractory acute myeloid leukaemia remains poor. Although encouraging, published paediatric data on venetoclax combined with intensive chemotherapy are scarce. We aimed to refine efficacy and toxicity estimates from the previously published dose-escalation phase of this study.
Methods: This multicentre, phase 1 study included two phases, an initial dose-escalation phase to identify the primary endpoint of recommended phase 2 dose (RP2D; previously reported), followed by an expansion cohort phase, the results of which are reported here. Paediatric patients (aged 2-24 years) with relapsed or refractory acute myeloid leukaemia from three US research hospitals were included. Patients had at least 5% blasts in the bone marrow by morphology or at least 1% blasts by flow cytometry. Treatment varied across cohorts. Patients received oral venetoclax 360 mg/m2 (maximum 600 mg) daily for 27 days after a 50% dose reduction on day 1 and intravenous cytarabine 1000 mg/m2 per dose every 12 h for eight doses on days 8-11 (cohort A), with intravenous idarubicin (12 mg/m2 on day 8; cohort B) and dexrazoxane or intravenous azacitidine (75 mg/m2 on days 1-7; cohort C). Here, we report results for all patients treated at the RP2D, including patients treated in the expansion cohort phase (cohort A and B) and patients in cohort C added by protocol amendment (Oct 13, 2020). This final report describes the key secondary endpoint of…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 44 participants or records.
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