Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome

Inclusion Criteria: * Diagnosis of MDS confirmed by bone marrow aspirate and/or biopsy within 6 weeks prior to first dose of study drug according to World Health Organization (WHO) or French-American-British (FAB) classification * MDS classified as Low risk or Int-1 risk (any cytogenetics) or Trisomy 8 Int-2 risk, according to IPSS classification * Transfusion dependency defined by at least 4 units of RBC administered within 8 weeks before baseline * Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, chemotherapy, immunosuppressive agents) for at least 4 weeks * ECOG performance status of 0, 1 or 2 Exclusion Criteria: * Ongoing clinically significant anemia due to factors such as iron, B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding, unless stabilized for 1 week after RBC transfusion * Serum ferritin \<50 ng/mL * Hypoplastic MDS (cellularity \<10%) * 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, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia * 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 * 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 (bHCG) pregnancy test at Screening * Major surgery without full recovery or major surgery within 3 weeks of rigosertib treatment start * Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic pressure ≥110 mmHg) * New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures * Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy * Chronic use (\>2 weeks) of corticosteroids (\>10 mg/24 hr equivalent prednisone) within 4 weeks of starting rigosertib * Investigational therapy within 4 weeks of starting rigosertib * Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements