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

2014-08-27 03:12:42 | BioPortfolio

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).

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Acute Myelogenous Leukemia

Intervention

TH-302

Location

University of Texas M.D. Anderson Cancer Center
Houston
Texas
United States
77030

Status

Recruiting

Source

Threshold Pharmaceuticals

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:42-0400

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Medical and Biotech [MESH] Definitions

A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.

An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.

An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.

Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria.

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