NCT01085656

A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory AML and MDS

A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is intended to determine the safety and maximum tolerated dose of a drug, OXi4503 (combretastatin A1 diphosphate, CA1P, OXiGENE), in patients with relapsed and refractory AML and MDS.

Detailed description

Despite initial disease remissions with cytotoxic chemotherapies, patients with AML and MDS often relapse and die of their disease. Novel strategies for targeting dependent pathways are needed. AML and MDS depend on blood vessels for survival and proliferation. OXi4503 is a novel microtubule targeting agent that selectively destroys cancer-associated blood vessels, induces cancer cell apoptosis via an ortho-quinone moiety and results in significant regressions of solid tumors. OXi4503 is currently being tested in phase I clinical trials of advanced solid tumors. In preclinical studies with human AML, OXi4503 was cytotoxic to leukemia cells, decreased size of chloromas, regressed leukemic cell engraftment in bone marrow and brought about phenotypic and molecular remissions. Given these results, we hypothesize that OXi4503 has disease remitting effects in myeloid malignancies such as AML and MDS. Before evaluating efficacy, safety and maximum tolerated dose of OXi4503 will be defined in AML and MDS patients. In addition, assessments of pharmacokinetic (PK) and pharmacokinetic (PD) parameters will be made, and relationships between dose and biologic activity will be defined. Results from this trial will provide new clinical data and biologic insight regarding the effects of OXi4503 in AML and MDS, and will serve as the basis for future efficacy trials.

Conditions

• Leukemia, Myelogenous, Acute
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
DRUG	OXi4503	Two safety cohorts treating two (2) patients at a dose of 2.5 mg/m2 followed by two patients at 3.75 mg/m2 will be completed prior to beginning at the dose level of 5 mg/m2. Dosing of OXi4503 will be an intravenous infusion (IV) over 10 minutes on Days 1, 8, 15, and 22 of each 28 day cycle. Dose escalations and de-escalations of 25% will be made until the maximum tolerated dose is reached. Number of cycles: After Cycle 1, subjects who achieve stable disease (SD) or greater response may continue to receive additional cycles of treatment until either disease progression (defined as greater than 25% increase in leukemia myeloblasts in the bone marrow compared to baseline examination) or unacceptable toxicity due to the investigational agent.

Timeline

• Start date: 2011-02-01
• Primary completion: 2016-01-01
• Completion: 2016-01-01
• First posted: 2010-03-12
• Last updated: 2017-08-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study