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).
Unknown status
Phase 1/Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Phase 1 - OXi4503 | CA1P, combretastatin A1-diphosphate | OXi4503 dose escalation |
| Phase 1 - OXi4503 + cytarabine | CA1P, combretastatin A1-diphosphate | OXi4503 + cytarabine dose escalation |
| Phase 2 - OXi4503 + cytarabine | CA1P, combretastatin A1-diphosphate | Phase 2 AML |
| Phase 2 - OXi4503 + cytarabine | CA1P, combretastatin A1-diphosphate | Phase 2 MDS |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Phase 2 AML | Experimental | OXi4503 at MTD plus cytarabine 1g/m2/day |
|
| Phase 2 MDS | Experimental | OXi4503 at MTD plus cytarabine 1g/m2/day |
|
| OXi4503 dose escalation | Experimental | MTD for OXi4503 will be determined |
|
| OXi4503 + cytarabine dose escalation | Experimental | MTD of the combination of OXi4503 + cytarbine will be determined |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Phase 1b:MTD of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: |
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Unknown status |
| Lead Sponsor: | Mateon Therapeutics |
June 4, 2018
