A Phase II, Multicenter, Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent Low or Intermediate-1 (Any Cytogenetics) or Trisomy 8 Intermediate-2 Myelodysplastic Syndrome Patients Based on IPSS Classification

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