Three Dosing Schedules of Oral Rigosertib in MDS Patients

Inclusion Criteria: * Diagnosis of MDS according to World Health Organization (WHO) criteria or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening. * MDS classified as Low-risk or Int-1 risk or Int-2 risk according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as High-risk since their MDS was diagnosed. * Transfusion dependency defined by transfusion of at least 4 units of RBC (red blood cells) within 8 weeks before Screening; pre-transfusion Hgb (hemoglobin) values must be ≤ 9 g/dL to be taken into account. * Refractory to 8- to 12-week course of ESA (erythropoiesis stimulating agent) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ˃ 500 mU/mL and off ESA for at least 8 weeks before Screening. * Off all other treatments for MDS for at least 2 weeks prior to Screening. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. * Willing to adhere to the prohibitions and restrictions specified in the protocol. * The patient must signed an informed consent form (ICF). Exclusion Criteria: * Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal bleeding. * 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. * Active infection not adequately responding to appropriate therapy. * Total bilirubin ≥ 2.0 mg/dL not related to hemolysis or Gilbert's disease. * Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x the 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 of child-bearing potential or male patients with partners of child-bearing potential who are unwilling to follow strict contraception requirements before entry and throughout the study, up to and including the 30-day non-treatment follow-up period. * Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening or who are lactating. * Major surgery without full recovery or major surgery within 3 weeks of Screening. * 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 chemotherapy, radiotherapy, or immunotherapy. * Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hour equivalent prednisone) within 4 weeks of Baseline/Cycle 1 Day 1 visit. * Investigational therapy within 4 weeks of Screening. * Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.