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

Sponsor

Mateon Therapeutics (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02576301

Collaborator

(none)

105

Enrollment

Locations

Arms

Duration (Months)

26.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia Myelodysplastic Syndromes	Drug: Phase 1 - OXi4503 Drug: Phase 1 - OXi4503 + cytarabine Drug: Phase 2 - OXi4503 + cytarabine Drug: Phase 2 - OXi4503 + cytarabine	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Oct 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2019

Anticipated Study Completion Date :

Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2 AML OXi4503 at MTD plus cytarabine 1g/m2/day	Drug: Phase 2 - OXi4503 + cytarabine Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with AML Other Names: CA1P combretastatin A1-diphosphate
Experimental: Phase 2 MDS OXi4503 at MTD plus cytarabine 1g/m2/day	Drug: Phase 2 - OXi4503 + cytarabine Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with MDS Other Names: CA1P combretastatin A1-diphosphate
Experimental: OXi4503 dose escalation MTD for OXi4503 will be determined	Drug: Phase 1 - OXi4503 Determination of MTD of OXi4503 Other Names: CA1P combretastatin A1-diphosphate
Experimental: OXi4503 + cytarabine dose escalation MTD of the combination of OXi4503 + cytarbine will be determined	Drug: Phase 1 - OXi4503 + cytarabine Determination of MTD of the combination of OXi4503 + cytarabine Other Names: CA1P combretastatin A1-diphosphate

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provide informed consent
≥ 18 years of age
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

Phase 2 (expansion) subjects must have either MDS or relapsed/refractory AML
Eastern Cooperative Oncology Group performance status 0, 1, or 2
Total bilirubin ≤ 2
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times upper limit of normal (ULN)
Serum creatinine < 2.5 times ULN
Prothrombin time (PT)/international normalized ratio and (PTT) in normal range ± 25%
Women of child-bearing potential
Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods

Exclusion Criteria:

Acute promyelocytic leukemia
Absolute peripheral blood myeloblast count greater than 20,000/mm3
Uncontrolled hypertension
History of congenital long QT syndrome or torsades de pointes
Pathologic bradycardia or heart block
Prolonged baseline QTc
Hiistory of ventricular arrhythmia
Myocardial infarction and/or new ST elevation
Any history of hemorrhagic stroke
Symptomatic congestive heart failure
Major hemorrhagic event within 28 days
Suggestive central nervous system involvement with leukemia
Any open wound
Pregnant and nursing subjects are excluded
Treatment with any anticancer therapy
Treatment with colchicine is excluded.
Psychiatric disorders that would interfere with consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
2	University of Florida	Gainesville	Florida	United States	32610
3	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
4	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas	United States	66205