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

NCT ID: NCT02576301

Last Updated: 2018-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2020-10-31

Brief Summary

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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

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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.

Conditions

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Acute Myelogenous Leukemia Myelodysplastic Syndromes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 2 AML

OXi4503 at MTD plus cytarabine 1g/m2/day

Group Type EXPERIMENTAL

Phase 2 - OXi4503 + cytarabine

Intervention Type DRUG

Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with AML

Phase 2 MDS

OXi4503 at MTD plus cytarabine 1g/m2/day

Group Type EXPERIMENTAL

Phase 2 - OXi4503 + cytarabine

Intervention Type DRUG

Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with MDS

OXi4503 dose escalation

MTD for OXi4503 will be determined

Group Type EXPERIMENTAL

Phase 1 - OXi4503

Intervention Type DRUG

Determination of MTD of OXi4503

OXi4503 + cytarabine dose escalation

MTD of the combination of OXi4503 + cytarbine will be determined

Group Type EXPERIMENTAL

Phase 1 - OXi4503 + cytarabine

Intervention Type DRUG

Determination of MTD of the combination of OXi4503 + cytarabine

Interventions

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Phase 1 - OXi4503

Determination of MTD of OXi4503

Intervention Type DRUG

Phase 1 - OXi4503 + cytarabine

Determination of MTD of the combination of OXi4503 + cytarabine

Intervention Type DRUG

Phase 2 - OXi4503 + cytarabine

Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with AML

Intervention Type DRUG

Phase 2 - OXi4503 + cytarabine

Safety and efficacy of the combination of OXi4503 + cytarabine in subjects with MDS

Intervention Type DRUG

Other Intervention Names

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CA1P combretastatin A1-diphosphate CA1P combretastatin A1-diphosphate CA1P combretastatin A1-diphosphate CA1P combretastatin A1-diphosphate

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mateon Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status RECRUITING

University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status RECRUITING

University of Kansas Cancer Center and Medical Pavilion

Westwood, Kansas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rachel Couchenour

Role: CONTACT

650-635-7000

Facility Contacts

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Bruck Habtemariam

Role: primary

310-794-0242

Christina Cline, RN

Role: primary

352-273-6840

Yvonne Dinh

Role: primary

305-243-9899

Michelle Cairns, MA

Role: primary

913-945-7547

References

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Johnson SP, Ogunlade O, Lythgoe MF, Beard P, Pedley RB. Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7436-7447. doi: 10.1158/1078-0432.CCR-19-0360. Epub 2019 Sep 24.

Reference Type DERIVED
PMID: 31551349 (View on PubMed)

Other Identifiers

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OX1222

Identifier Type: -

Identifier Source: org_study_id

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