A Phase 1b Dose Escalation Study of OXi4503 as a Single Agent and in Combination with Cytarabine with Subsequent Combination Phase 2 Cohorts for Subjects with Relapsed/Refractory Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS)

Inclusion Criteria:

1. Provide informed consent
2. ≥ 18 years of age

3. Phase 1 (dose escalation) subjects must have either:

   • AML that has failed to achieve complete remission or morphologic complete remission or
   • MDS - Marrow blasts must be > 5% and disease failed at least 1 prior hypomethylating agent
4. Phase 2 (expansion) subjects must have either MDS or relapsed/refractory AML
5. Eastern Cooperative Oncology Group performance status 0, 1, or 2
6. Total bilirubin ≤ 2
7. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times upper limit of normal (ULN)
8. Serum creatinine < 2.5 times ULN
9. Prothrombin time (PT)/international normalized ratio and (PTT) in normal range ± 25%
10. Women of child-bearing potential
11. Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods

Exclusion Criteria:

1. Acute promyelocytic leukemia
2. Absolute peripheral blood myeloblast count greater than 20,000/mm3
3. Uncontrolled hypertension
4. History of congenital long QT syndrome or torsades de pointes
5. Pathologic bradycardia or heart block
6. Prolonged baseline QTc
7. Hiistory of ventricular arrhythmia
8. Myocardial infarction and/or new ST elevation
9. Any history of hemorrhagic stroke
10. Symptomatic congestive heart failure
11. Major hemorrhagic event within 28 days
12. Suggestive central nervous system involvement with leukemia
13. Any open wound
14. Pregnant and nursing subjects are excluded
15. Treatment with any anticancer therapy
16. Treatment with colchicine is excluded.
17. Psychiatric disorders that would interfere with consent