Vosaroxin for Intermediate 2 or High-risk MDS After Failure With Hypomethylating Agent-based Therapy

Inclusion Criteria: * Able to understand and to provide written informed consent * At least 18 years of age with pathologically confirmed MDS (\< 20% blasts in bone marrow, peripheral blood, or both) by WHO classification with an intermediate 2 or high-risk score assessed by IPSS (score ≥ 1.5) * Must have received at least 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy and are either refractory to, relapsed after, or are intolerant of prior therapy with either agent. 1. Primary failure/refractory: Stable or worsening disease after a minimum of 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy 2. Secondary failure/relapse: Bone marrow blast count increase or loss of hematologic response after initial treatment response with hypomethylating agent-based therapy 3. Intolerance: Intolerance of hypomethylating agent-based therapy regardless of number of cycles completed and clinical response * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 * Must have a life expectancy of at least 2 months * Must demonstrate adequate clinical laboratory values (based on local laboratory results) as follows: 1. Serum creatinine 1.5 ≤ x the upper limit of normal (ULN) or calculated creatinine clearance (CLCR) of ≥ 50 mL/min 2. Total bilirubin ≤ 1.5 x ULN, higher levels are acceptable if these can be attributed to active hemolysis (as indicated by positive Coomb's test, decreased haptoglobin, Gilbert's disease, elevated indirect bilirubin, and/or lactate dehydrogenase) or ineffective erythropoiesis (as indicated by bone marrow findings). 3. Aspartate aminotransferase (AST) ≤ 2.5 x ULN 4. Alanine aminotransferase (ALT) ≤ 2.5 x ULN 5. Must show adequate cardiac function defined as a left ventricular ejection fraction (LVEF) * 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan * Must have acceptable recovery from clinically significant non-hematologic toxicity after prior therapy * Must be infertile or agree to use an effective contraceptive method for the duration of the study and for 30 days after the last dose (for men and women of child-producing potential). Exclusion Criteria: * Patients meeting any of the following criteria are excluded: * Presence of AML (≥ 20% blasts in bone marrow, peripheral blood, or both) * Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results. * Have known active central nervous system disease or active, uncontrolled, clinically significant infection(s). * Have other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before enrollment, except nonmelanoma skin cancer or cervical intraepithelial neoplasia * Have experienced CTCAE Grade 2 or greater oral mucositis within the last 14 days * Are receiving any other investigational therapy or protocol-prohibited therapy * Have received previous treatment with vosaroxin * Pregnant or breastfeeding females * Known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin) * Treatment with any anticancer therapy (including radiation) within the previous 14 days prior to the first dose of study drug or less than full recovery (CTCAE grade 1) from the clinically significant toxic effects of that treatment. * Treatment with any investigational drugs within the previous 14 days prior to Cycle 1, Day 1 or ongoing adverse events from previous cancer treatment with investigational drugs, regardless of the time period. * Have any other medical, psychological, or social condition that, in the opinion of the PI, would contraindicate the patient's participation in the clinical study due to safety or compliance with clinical study procedures