Abstract CT307: Phase I/II study of vosaroxin and decitabine in older patients (pts) with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS)
Authors: Daver Naval , Kantarjian Hagop M. , Garcia - Manero Guillermo , Pemmaraju Naveen , Kadia Tapan , DiNardo Courtney , Jain Nitin , Borthakur Gautum , Cortes Jorge , Adam Craig , Ravandi Farhad 
Published: May 2015

Abstract
Background: Vosaroxin (formerly voreloxin), is a quinolone derived DNA topoisomerase II inhibitor, which is not a substrate for p53 or P-glycoprotein and has limited toxicity; it is currently under evaluation for the treatment of pts with AML and high-risk MDS.
Methods: Pts were eligible if they had AML or high-risk MDS (defined as having ≥ 10% blasts in the bone marrow), were 60 years of age or older, and had adequate performance status (ECOG ≤ 2) and organ function. Pts younger than 60 who were unsuitable for standard chemotherapy were also eligible. The treatment regimen included vosaroxin 90 mg/m2 daily on days 1 and 4 with decitabine 20 mg/m2 daily for 5 days. Vosaroxin dose was reduced to 70 mg/m2 in consolidation cycles, which were repeated in approximately 4 to 5-week intervals for a total of up to 7 cycles. Dose adjustments and dose delays of one or both agents, were allowed based on toxicity. The primary endpoint was to determine the complete remission (CR) rate. Secondary endpoints were: CR duration, disease-free survival, overall survival, safety, and early mortality.
Results: To date, 12 pts (9 AML, 3 high-risk MDS) with a median age of 71 years (range, 41-76) have been enrolled; 11 were older than 60 years. They included 6 (50%) pts with diploid cytogenetics, 4 (34%) with complex cytogenetic abnormalities including chromosome 5 and/or 7 abnormalities, and 2 (16%) with other miscellaneous abnormalities. 4 (34%) pts with AML had antecedent hematological disorders (AHD) including 1 (8%) with MDS, 1 (8%) with myeloproliferative neoplasm and 2 (17%) with MDS/MPN. Three pts with AHD had received prior therapy including 5-azacytidine (n=1), ruxolitinib + 5-azacytidine (n=1) and lenalidomide (n=1). RAS mutations were identified in 4 (34%) and IDH2 mutations in 2 (16%) pts. Median bone marrow blast %, median white blood cell, hemoglobin, & platelet counts were 29% (11-73), 3.7 x 109/L (1.0-127.1), 9.5 g/dL (8.2-10.8), and 92 x 109/L (11-361), respectively. 9 pts were evaluable for response; 5 (42%) achieved CR, 1 (8%) CRp, and 2 (17%) CRi, for an overall response rate of 89%. 1 pt had no response after cycle 1 and is currently undergoing re-induction. Three are too early for response assessment. Pts have received a median of 2 (1-3) treatment cycles with median number of cycles to response being 1 (1-2) and median time to achieving response, 26 days (21-74 days). The median duration of CR/CRp/CRi is 53+ days (6-89+ days). One pt has proceeded to allogeneic stem cell transplant. No pts died during induction. One pt died on study on day 47 from sepsis and acute myocardial infarction. The regimen is well tolerated with the main grade ≥ 3 toxicity being mucositis in 3 (25%) pts.
Conclusion: Combination of vosaroxin and decitabine is effective and well tolerated in older patients with AML and high-risk MDS. Enrollment is ongoing.
Citation Format: Naval Daver, Hagop M. Kantarjian, Guillermo Garcia - Manero, Naveen Pemmaraju, Tapan Kadia, Courtney DiNardo, Nitin Jain, Gautum Borthakur, Jorge Cortes, Craig Adam, Farhad Ravandi. Phase I/II study of vosaroxin and decitabine in older patients (pts) with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT307. doi:10.1158/1538-7445.AM2014-CT307