Dose Escalation of OXi4503 as Single Agent and Combination With Cytarabine w/Subsequent Ph 2 Cohorts for AML and MDS

Ph 1b Dose Escalation Study of OXi4503 as a Single Agent and in Combination With Cytarabine With Subsequent Phase 2 Cohorts for Subjects With Relapsed/Refractory Acute AML and MDS

Phase 1 will investigate maximum tolerated dose of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS.

Phase 2 will investigate overall response rate of OXi4503 in combination with intermediate-dose cytarabine in 1) subjects with MDS after failure of 1 prior hypomethylating agent (Arm A) and 2) subjects with relapsed and refractory AML after treatment failure of up to 1 prior chemotherapy regimen (Arm B).

Phase 1 dose escalation component will assess the safety, PK/PD, and preliminary efficacy of OXi4503 as a single agent in subjects with relapsed/refractory AML and MDS, and the safety and PK/PD of the combination of OXi4503 with intermediate-dose cytarabine in subjects with AML/MDS.

Phase 2 will assess the preliminary efficacy of the OXi4503+cytarabine combination in 2 cohorts.

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