Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with refractory or relapsed acute myeloid leukaemia (AML)—An open-label, phase I/II study

Bisantrene (Bis), an anthracene derivative with topoisomerase-II inhibitory activity and low cardiotoxicity, may enhance its efficacy when combined with nucleoside analogues such as clofarabine (Clo) and fludarabine (Flu) in preclinical acute myeloid leukaemia (AML) studies. We conducted a phase I/II open-label study (NCT04989335) to evaluate the safety and efficacy of Bis/Clo/Flu in relapsed/refractory AML. Twenty-one patients (median age: 47 years, 55% female) received Flu (10 mg/m²), Clo (30 mg/m²) and Bis (250 mg/m²) intravenously for 4 days. Sixteen had relapsed post-allogeneic stem cell transplantation, and six had extramedullary disease (EMD). Liver toxicity occurred in 10 patients but resolved. No significant cardiac toxicity was observed. Efficacy was assessable in 15 patients, while in six patients, it could not be evaluated due to early non-relapse mortality occurring within 30 days of treatment initiation, before the first post-treatment assessment. Six of the 15 patients responded: five achieved complete remission, and one with EMD achieved a partial remission, yielding a 40% response rate. Responses were transient, but six patients, including four undergoing second allo-HSCTs, proceeded to allo-HSCT within 1–3 months post-treatment. The Bis/Clo/Flu regimen demonstrated a tolerable safety profile and potential as a bridging therapy in high-risk, heavily pretreated AML.