Study of Hypoxia-Activated Prodrug TH-302 to Treat Advanced Leukemias
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01149915|
Recruitment Status : Completed
First Posted : June 24, 2010
Last Update Posted : May 7, 2015
|Condition or disease||Intervention/treatment||Phase|
|Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Chronic Myelogenous Leukemia High-risk Myelodysplastic Syndrome Chronic Lymphocytic Leukemia Advanced Myelofibrosis||Drug: TH-302||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||June 2010|
|Actual Primary Completion Date :||August 2013|
|Actual Study Completion Date :||August 2013|
- 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.
- To determine the maximum tolerated dose of TH-302 [ Time Frame: 2 years ]
- To determine the dose-limiting toxicity of TH-302 [ Time Frame: 2 years ]
- TO determine the number of participants with Adverse Events as a measure of safety and tolerability [ Time Frame: 2 years ]
- To determine the efficacy of TH-302 via specific response criteria [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01149915
|United States, Texas|
|University of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Marina Konopleva, MD, PhD||M.D. Anderson Cancer Center|