Back to results

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

Primary Purpose

Acute Myelogenous Leukemia, Myelodysplastic Syndromes

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Phase 1 - OXi4503

Phase 1 - OXi4503 + cytarabine

Phase 2 - OXi4503 + cytarabine

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring AML, MDS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

David Geffen School of Medicine at UCLARecruiting
University of FloridaRecruiting
University of Miami Sylvester Comprehensive Cancer CenterRecruiting
University of Kansas Cancer Center and Medical PavilionRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Phase 2 AML

Phase 2 MDS

OXi4503 dose escalation

OXi4503 + cytarabine dose escalation

Arm Description

OXi4503 at MTD plus cytarabine 1g/m2/day

MTD for OXi4503 will be determined

MTD of the combination of OXi4503 + cytarbine will be determined

Outcomes

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02576301

First Posted

October 13, 2015

Last Updated

June 1, 2018

Sponsor

Mateon Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT02576301

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

October 2019 (Anticipated)

Study Completion Date

October 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mateon Therapeutics

4. Oversight

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myelogenous Leukemia, Myelodysplastic Syndromes

Keywords

AML, MDS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

105 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Phase 2 AML

Arm Type

Experimental

Arm Description

OXi4503 at MTD plus cytarabine 1g/m2/day

Arm Title

Phase 2 MDS

Arm Type

Experimental

Arm Description

OXi4503 at MTD plus cytarabine 1g/m2/day

Arm Title

OXi4503 dose escalation

Arm Type

Experimental

Arm Description

MTD for OXi4503 will be determined

Arm Title

OXi4503 + cytarabine dose escalation

Arm Type

Experimental

Arm Description

MTD of the combination of OXi4503 + cytarbine will be determined

Intervention Type

Drug

Intervention Name(s)

Phase 1 - OXi4503

Other Intervention Name(s)

CA1P, combretastatin A1-diphosphate

Intervention Description

Determination of MTD of OXi4503

Intervention Type

Drug

Intervention Name(s)

Phase 1 - OXi4503 + cytarabine

Other Intervention Name(s)

CA1P, combretastatin A1-diphosphate

Intervention Description

Determination of MTD of the combination of OXi4503 + cytarabine

Intervention Type

Drug

Intervention Name(s)

Phase 2 - OXi4503 + cytarabine

Other Intervention Name(s)

CA1P, combretastatin A1-diphosphate

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Phase 2 - OXi4503 + cytarabine

Other Intervention Name(s)

CA1P, combretastatin A1-diphosphate

Intervention Description

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

Primary Outcome Measure Information:

Title

Phase 1b:MTD of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS

Time Frame

1 year

Title

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rachel Couchenour

Phone

650-635-7000

Facility Information:

Facility Name

David Geffen School of Medicine at UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bruck Habtemariam

Phone

310-794-0242

bhabtemariam@mednet.ucla.edu

First Name & Middle Initial & Last Name & Degree

Gary Schiller, MD

Facility Name

University of Florida

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christina Cline, RN

Phone

352-273-6840

clcline@ufl.edu

First Name & Middle Initial & Last Name & Degree

Christopher Cogle R Cogle, MD

Facility Name

University of Miami Sylvester Comprehensive Cancer Center

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yvonne Dinh

Phone

305-243-9899

y.dinh@med.miami.edu

First Name & Middle Initial & Last Name & Degree

Justin Watts, MD

Facility Name

University of Kansas Cancer Center and Medical Pavilion

City

Westwood

State/Province

Kansas

ZIP/Postal Code

66205

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michelle Cairns, MA

Phone

913-945-7547

mcairns3@kumc.edu

First Name & Middle Initial & Last Name & Degree

Tara Lin, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

31551349

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs