NCT01149915

Study of Hypoxia-Activated Prodrug TH-302 to Treat Advanced Leukemias

A Phase I Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of TH-302, a Hypoxia-Activated Prodrug, in Patients With Advanced Leukemias

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Threshold Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this study is to determine the maximum tolerated dose, dose limiting toxicity, safety and tolerability of TH-302 in patients with acute leukemias, advanced phase chronic myelogenous leukemia (CML), high risk myelodysplastic syndromes, advanced myelofibrosis or relapsed/refractory chronic lymphocytic leukemia (CLL).

Detailed description

Tumor hypoxia has been associated with resistance to chemotherapy and radiotherapy (Brown et al, 2004; Boyle 2006). TH-302, a hypoxia activated prodrug (HAP), exploits the hypoxic nature of tumors while having little or no effect on normal tissue. TH-302 belongs to a class of alkylating agents called oxazaphosphorines which have major experimental and clinical activity (Brock 1989). Since TH-302 is selectively targeted to the hypoxic microenvironment, this agent may represent an improvement over other agents in this class. Preclinical data support the hypothesis that TH-302 targets hypoxic regions of tumors and also is able to kill other tumor cells in normoxic regions as a result of cytotoxin diffusion, leading to significant effects on tumor growth. Preclinical data has shown that TH-302 has anti-tumor activity in multiple myeloma cells in vivo and in vitro. Additional preclinical data demonstrated the marked expansion of the hypoxic bone marrow areas in diseased mice with ALL. These results suggest that this agent may be useful in treating advanced leukemias. The drug is stable in plasma and liver, does not appear to be at risk for drug-drug interactions, and has mild, reversible toxicities. In this dose-escalation study, patients with advanced leukemias will receive infusions of TH-302 to determine the maximum tolerated dose.

Conditions

• Acute Myelogenous Leukemia
• Acute Lymphoblastic Leukemia
• Chronic Myelogenous Leukemia
• High-risk Myelodysplastic Syndrome
• Chronic Lymphocytic Leukemia
• Advanced Myelofibrosis

Interventions

Type	Name	Description
DRUG	TH-302	TH-302 will be administered as a 30-minute intravenous infusion daily for 5 days every 21 days. Patients who successfully complete a 3-week treatment cycle without evidence of significant treatment-related toxicity or clinically significant progressive disease will continue to receive treatment for up to six cycles.

Timeline

• Start date: 2010-06-01
• Primary completion: 2013-08-01
• Completion: 2013-08-01
• First posted: 2010-06-24
• Last updated: 2015-05-07

Locations

1 site across 1 country: United States