Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine

Exclusion Criteria

• •Off all other treatments for MDS for at least 4 weeks, except for azacitidine or decitabine. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated.
• •No medical need for induction chemotherapy.
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• •Willing to adhere to the prohibitions and restrictions specified in this protocol.
• •Patient must signed an informed consent form.
• •Previous participation in a clinical study of IV or oral rigosertib.
• •Anemia due to factors other than MDS (including hemolysis or gastrointestinal \[GI\] bleeding) unless stabilized for 1 week after RBC transfusion.
• •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.
• •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, or 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 (βHCG) pregnancy test at Screening.
• •Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 visit.
• •Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic pressure ≥ 110 mmHg).
• •New onset seizures (within 3 months prior to Baseline) or poorly controlled seizures.
• •Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
• •Prior treatment with low-dose cytarabine during the past 2 years.
• •Investigational therapy within 4 weeks of Baseline/Day 1 visit.
• •Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.