Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine

Inclusion Criteria: * Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or French-American-British (FAB) classification. * MDS classified as follows, according to WHO criteria and FAB classification: * RAEB-1 (5% to 9% BM blasts) * RAEB-2 (10% to 19% BM blasts) * CMML (10% to 20% BM blasts) and white blood cells (WBC) \< 13,000/μL * RAEB-t (20% to 30% BM blasts), meeting the following criteria: WBC \< 25,000/μL at study entry; or, Stable White Blood Cell (WBC) at least 4 weeks prior to Screening and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukopheresis. * At least one cytopenia (Absolute Neutrophil Count (ANC) \< 1800/μL or Platelet (PLT) count \< 100,000/μL or hemoglobin (Hgb) \< 10 g/dL). * Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows: * For patients with ˂ 5% BMBL, ≥ 50% increase in BMBL to ˃ 5% BMBL * For patients with 5-10% BMBL, ≥ 50% increase in BMBL to ˃ 10% BMBL * For patients with 10-20% BMBL, ≥ 50% increase in BMBL to ˃ 20% BMBL * For patients with 20-30% BMBL, ≥ 50% increase in BMBL to ˃ 30% BMBL * Any of the following: ≥ 50% decrease from maximum remission/response levels in granulocytes or PLT; Decrease in Hgb concentration by ≥ 2 g/dL; or, Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values ˂ 9 g/dL prior to transfusion to be considered), in the absence of another explanation. * Has failed to respond to, relapsed following, not eligible, or opted not to participate in bone marrow transplantation. * Off all other treatments for MDS for at least 4 weeks, except for azacitidine or decitabine. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated. * No medical need for induction chemotherapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. * Willing to adhere to the prohibitions and restrictions specified in this protocol. * Patient must signed an informed consent form. Exclusion Criteria: * Previous participation in a clinical study of IV or oral rigosertib. * Anemia due to factors other than MDS (including hemolysis or gastrointestinal \[GI\] bleeding) unless stabilized for 1 week after RBC transfusion. * Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast. * Uncontrolled intercurrent illness including. * Active infection not adequately responding to appropriate therapy. * Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease. * ALT/AST ≥ 2.5 x upper limit of normal (ULN). * Serum creatinine ≥ 2.0 mg/dL. * Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<130 mEq/L). * Female patients who are pregnant or lactating. * Patients who are unwilling to follow strict contraception requirements. * Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (βHCG) pregnancy test at Screening. * Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 visit. * Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic pressure ≥ 110 mmHg). * New onset seizures (within 3 months prior to Baseline) or poorly controlled seizures. * Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy. * Prior treatment with low-dose cytarabine during the past 2 years. * Investigational therapy within 4 weeks of Baseline/Day 1 visit. * Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.