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

Phase 1

• Conditions: Acute Myelogenous Leukemia; Myelodysplastic Syndromes
• Interventions: Drug: Phase 2 - OXi4503 + cytarabine; Drug: Phase 1 - OXi4503; Drug: Phase 1 - OXi4503 + cytarabine

• Registration Number: NCT02576301
• Lead Sponsor: Mateon Therapeutics

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.

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2015-10-13
• Study First Submitted QC: 2015-10-14
• Study First Posted: 2015-10-15
• Status Verified: 2017-09
• Last Update Submitted: 2018-06-01
• Last Update Posted: 2018-06-04
• Primary Completion: 2019-10
• Study Completion: 2020-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 105

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase 2 MDS	Phase 2 - OXi4503 + cytarabine	OXi4503 at MTD plus cytarabine 1g/m2/day
OXi4503 dose escalation	Phase 1 - OXi4503	MTD for OXi4503 will be determined
OXi4503 + cytarabine dose escalation	Phase 1 - OXi4503 + cytarabine	MTD of the combination of OXi4503 + cytarbine will be determined
Phase 2 AML	Phase 2 - OXi4503 + cytarabine	OXi4503 at MTD plus cytarabine 1g/m2/day

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (4)

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

University of Kansas Cancer Center and Medical Pavilion; 🇺🇸 Westwood, Kansas, United States