Randomized Study of ON 01910.Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts

Inclusion Criteria:

   - MDS diagnosis confirmed within 6 weeks prior to entry according to WHO or FAB
   classification

   - MDS classified as follows, according to WHO and FAB classification:

      - RAEB-1 (5% - 9% BM blasts)

      - RAEB-2 (10% - 19% BM blasts)

      - CMML (10% - 20% BM blasts) and WBC < 13,000/μL

      - RAEB-t (20% - 30% BM blasts), with following criteria:

      - o WBC < 25 x 10E9/L at entry

      - o Stable WBC at least 4 weeks prior to entry and not requiring intervention for
      WBC control with hydroxyurea, chemotherapy, or leukopheresis.

   - At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin <10
   g/dL)

   - Progression according to 2006 International Working Group (IWG) criteria any time
   after start of azacitidine or decitabine during past 2 years; or failure to achieve
   complete or partial response or hematological improvement (according to 2006 IWG)
   after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine
   during past 2 years; or relapse after initial complete or partial response or
   hematological improvement (according to 2006 IWG criteria) observed after at least six
   4-week cycles of azacitidine or four 6-week cycles of decitabine during past 2 years;
   or, intolerance to azacitidine or decitabine defined by drug-related ≥Grade 3 liver or
   renal toxicity leading to discontinuation during the past 2 years.

   - Did not respond to, relapsed after, not eligible for, or opted not to do bone marrow
   transplantation

   - Off other MDS treatments for at least 4 weeks; Filgrastim (G-CSF) and erythropoietin
   allowed before and during the study as clinically indicated.

   - No need for induction chemotherapy

   - ECOG status 0, 1 or 2

   - Willing to adhere to protocol prohibitions and restrictions

   - Patient (or a legally authorized representative) must sign informed consent form to
   indicate patient's understanding study's purpose and procedures and willingness to
   participate

Exclusion Criteria:

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

   - Alanine transaminase (ALT)/aspartate transaminase (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)

   - Pregnant or lactating females

   - Patients unwilling to follow strict contraception requirements (including condom use
   for males with sexual partners, and for females: prescription oral contraceptives
   [birth control pills], contraceptive injections, intrauterine device, double-barrier
   method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or
   surgical sterilization) before entry and throughout the study

   - Females with reproductive potential who do not have a negative urine beta-human
   chorionic gonadotropin 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 systolic pressure ≥160 mmHg and/or diastolic
   pressure ≥110 mmHg)

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

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

   - Prior treatment with low-dose cytarabine during past 2 years Investigational therapy
   within 4 weeks of starting ON 01910.Na

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