Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk

Inclusion Criteria:

   - Diagnosis of MDS confirmed within 2 weeks prior to study entry according to the World
   Health Organization (WHO) Criteria or the French-American-British (FAB)
   Classification.

   - Trisomy 8 cytogenetics (simple or combined to other karyotypes) or patient classified
   as Intermediate-1 with bone marrow blasts equal to or greater than 5%, Intermediate-2
   or High Risk MDS according to the IPSS score, or Patients with peripheral blood blasts
   equal to or greater than 5%.

   - At least one cytopenia (Absolute Neutrophil Count < 1800/µl or Platelet Count
   <100,000/µl or Hemoglobin < 10 g/dL).

   - Failure of, or insufficient response to Azacytidine or Decitabine administered for 4
   to 6 cycles in patients classified as Intermediate-2 or High risk or to Erythrocyte
   stimulating agents (failure or insufficient response defined as transfusion dependence
   or Hemoglobin remaining below 10 g/dl) in Low or Intermediate-1 Risk Trisomy 8
   patients.

   - Failed to respond to, relapsed following, or opted not to participate in bone marrow
   transplantation.

   - Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for
   at least four weeks. As an exception, filgrastim (G-CSF) can be used before, during
   and after the protocol treatment for patients with documented febrile neutropenia (<
   500/µl).

   - ECOG Performance Status 0, 1 or 2.

   - Willing to adhere to the prohibitions and restrictions specified in this protocol.

   - Patient (or his/her legally authorized representative) must have signed an informed
   consent document indicating that he/she understands the purpose of and procedures
   required for the study and is willing to participate in the study.

Exclusion Criteria:

   - Anemia due to factors other than MDS (including hemolysis or gastrointestinal
   bleeding).

   - 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.

   - History of HIV-1 seropositivity.

   - 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 or AST
   > 2 X ULN.

   - Serum creatinine > 2.0 mg/dL or calculated creatinine clearance < 60 ml/min/1.73 m^2.

   - Ascites requiring active medical management including paracentesis, or hyponatremia
   (defined as serum sodium value of <134 Meq/L).

   - Women patients who are pregnant or lactating; Male patients with female sexual
   partners who are unwilling to follow the strict contraception requirements described
   in this protocol; Patients who do not agree to use adequate contraceptive [including
   prescription oral contraceptives (birth control pills), contraceptive injections,
   intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with
   condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry
   and throughout the study; Female patients with reproductive potential who do not have
   a negative serum beta-HCG pregnancy test at screening.

   - Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na
   treatment start.

   - Uncontrolled hypertension (defined as a systolic pressure equal to or greater than 160
   mmHg and/or a diastolic pressure equal to or greater than 110 mmHg).

   - New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly
   controlled seizures

   - Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy.

   - Treatment with standard MDS therapies or investigational therapy within 4 weeks of
   starting ON 01910.Na.

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