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

Myelodysplastic Syndromes Clinical Trial

— AML  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02576301
• Other study ID #: OX1222
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 2015
• Est. completion date: October 2020

Study information

• Verified date: September 2017
• Source: Mateon Therapeutics
• Contact: Rachel Couchenour
• Phone: 650-635-7000
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: October 2020
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Phase 1 - OXi4503
Determination of MTD of OXi4503
• Phase 1 - OXi4503 + cytarabine
Determination of MTD of the combination of OXi4503 + cytarabine
• Phase 2 - OXi4503 + cytarabine
Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with AML
• Phase 2 - OXi4503 + cytarabine
Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with MDS

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Mateon Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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