Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

Mike Dennis, Nigel Russell, Robert K Hills, Claire Hemmaway, Nicki Panoskaltsis, Mary-Frances McMullin, Lars Kjeldsen, Helen Dignum, Ian F Thomas, Richard E Clark, Don Milligan, Alan K Burnett

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36 Citations (Scopus)

Abstract

The development of new treatments for older patients with acute myeloid leukemia is an active area, but has met with limited success. Vosaroxin, a quinolone-derived intercalating agent has several properties that 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 cytarabine (Ara-C). To evaluate vosaroxin, we performed 2 randomized comparisons within the "Pick a Winner" program. A total of 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 (complete recovery [CR]/complete recovery with incomplete count recovery [CRi], 26% vs 30%; odds ratio [OR], 1.16 (0.49-2.72); P = .7) nor 12-month survival (12% vs 31%; hazard ratio [HR], 1.94 [1.26-3.00]; P = .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 = .6) nor survival (33% vs 37%; HR, 1.30 [0.81-2.07]; P = .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 randomization. At its first interim analysis, the Data Monitoring and Ethics Committee recommended closure of the vosaroxin-containing trial arms because a clinically relevant benefit was unlikely.

Original languageEnglish
Pages (from-to)2923-32
Number of pages10
JournalBlood
Volume125
Issue number19
DOIs
Publication statusPublished - 07 May 2015

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    Dennis, M., Russell, N., Hills, R. K., Hemmaway, C., Panoskaltsis, N., McMullin, M-F., Kjeldsen, L., Dignum, H., Thomas, I. F., Clark, R. E., Milligan, D., & Burnett, A. K. (2015). Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia. Blood, 125(19), 2923-32. https://doi.org/10.1182/blood-2014-10-608117