A randomised assessment of vosaroxin and vosaroxin combined with low dose Ara-C (LDAC) versus low dose Ara-C alone in older patients with acute myeloid leukemia.
AffiliationDepartment of Haematology, Christie Hospital, Manchester, United Kingdom
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AbstractThe development of new treatments for older patients with Acute Myeloid Leukaemia (AML) is an active area, but has met with limited success. Vosaroxin, a quinolone derived intercalating agent has several properties which could prove beneficial. Initial clinical studies showed it to be well tolerated in older patients with relapsed/refractory disease. In vitro data suggested synergy with Ara-C. To evaluate vosaroxin, we performed two randomised comparisons within the "Pick A Winner" Programme. 104 patients were randomized to vosaroxin vs low dose Ara-C (LDAC) and 104 to vosaroxin+LDAC vs LDAC. When comparing vosaroxin with LDAC neither response rate (CR/CRi), (26% vs 30%; odds ratio (OR) 1.16 (0.49-2.72) p=0.7) nor 12-month survival (12% vs 31%; hazard ratio (HR) 1.94 (1.26-3.00) p=0.003) showed benefit for vosaroxin. Likewise, in the vosaroxin+LDAC vs LDAC comparison, neither response rate (CR/CRi 38% vs 34%; OR 0.83 (0.37-1.84) p=0.6), nor survival (33% vs 37%, HR 1.30 (0.81-2.07) p=0.3) was improved. A major reason for this lack of benefit was excess early mortality in the vosaroxin+LDAC arm, most obviously in the second month following randomisation. At its first interim analysis, the Data Monitoring and Ethics Committee recommended closure of the vosaroxin-containing trial arms as a clinically relevant benefit was unlikely.
CitationA randomised assessment of vosaroxin and vosaroxin combined with low dose Ara-C (LDAC) versus low dose Ara-C alone in older patients with acute myeloid leukemia. 2015: Blood