Acute Myelogenous Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
AML, MDS
Brief summary
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).
Detailed description
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.
Interventions
DRUGPhase 1 - OXi4503
Determination of MTD of OXi4503
DRUGPhase 1 - OXi4503 + cytarabine
Determination of MTD of the combination of OXi4503 + cytarabine
DRUGPhase 2 - OXi4503 + cytarabine
Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with AML
Sponsors
Mateon Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b:MTD of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS | 1 year |
| Phase 2: Overall response rate of OXi4503 in combination with intermediate-dose cytarabine in subjects with MDS after failure of 1 prior hypomethylating agent (Arm A), and subjects with relapsed and refractory AML after treatment failure of up | 2 years |
Countries
United States
Contacts
Primary ContactRachel Couchenour
Outcome results
None listed