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

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