Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs

Inclusion Criteria:

   - Diagnosis of MDS according to World Health Organization (WHO) criteria (Appendix 2) or
   French-American-British (FAB) classification that must be confirmed by bone marrow
   (BM) aspirate and/or biopsy within 6 weeks prior to Screening.

   - Myelodysplastic syndrome (MDS) classified as Low risk or Int-1 risk, according to
   International Prognostic Scoring System (IPSS) classification; in addition, patients
   should never have been classified as Int-2 or High-risk since their MDS was diagnosed;

   - Transfusion dependency defined by transfusion of at least 4 units of Red blood cells
   (RBC) within 56 days before Screening (pre-transfusion Hgb values values must be ≤ 9
   g/dL to be taken into account).

   - Refractory to 8- to 12-week course of Erythropoiesis-stimulating agent (ESA)
   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 (azacitidine, decitabine, lenalidomide, chemotherapy,
   immunotherapy) 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 this protocol.

   - The patient must signed an informed consent form (ICF) indicating that s/he
   understands the purpose of, and procedures required for, the study and is willing to
   participate.

Exclusion Criteria:

   - Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or
   folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI)
   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 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 ≥ 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 who are pregnant or lactating.

   - Patients of childbearing potential who are unwilling to follow strict contraception
   requirements.

   - Female patients with reproductive potential who do not have a negative blood or urine
   pregnancy test at Screening.

   - 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 investigational agent or chemotherapy, radiotherapy, or
   immunotherapy.

   - Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hr equivalent prednisone)
   within 4 weeks of Screening.

   - Investigational therapy within 4 weeks of Screening.

   - Allergy to a local anaesthetic.

   - Psychiatric illness or social situation that would limit the patient's ability to
   tolerate and/or comply with study requirements.