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.

Abstract

The 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.