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

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

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.

• Journal Article Type: Article
• Acceptance Date: Mar 6, 2015
• Online Publication Date: May 7, 2015
• Publication Date: May 7, 2015
• Deposit Date: Jul 12, 2017
• Journal: Blood
• Print ISSN: 0006-4971
• Electronic ISSN: 1528-0020
• Publisher: American Society of Hematology
• Peer Reviewed: Peer Reviewed
• Volume: 125
• Issue: 19
• Pages: 2923-2932
• DOI: https://doi.org/10.1182/blood-2014-10-608117
• Public URL: https://nottingham-repository.worktribe.com/output/1112718
• Publisher URL: https://ashpublications.org/blood/article/125/19/2923/34272/Vosaroxin-and-vosaroxin-plus-low-dose-Ara-C-LDAC
• PMID: 25805811