The Oncology Service at the University of Missouri Veterinary Health Center is seeking canine patients with B cell lymphoma for a clinical trial. The study will evaluate the safety and efficacy of agents that modify gene expression (6-thioguanine or azacitidine) when used prior to standard chemotherapy.
Currently, remission duration and survival time in dogs with lymphoma has remained static when receiving multi-agent chemotherapy. The investigators hope using these drugs in an altered fashion from standard chemotherapy protocols will be safe in dogs and elongate remission durations and survival times. The researchers also expect to find new roles for these drugs in lymphoid diseases in both dogs and people.
These two agents modify gene expression by demethylating DNA. DNA methylation is one way cells can alter how their genes are expressed, without changing the DNA itself. Epigenetic modifications allow cells in the body to terminally differentiate into all of our different organs, with the exact same copy of DNA. However, some epigenetic changes can have damaging effects that result in diseases like cancer.
“Recent literature has shown the similarities between canine diffuse large B-cell lymphoma (DLBCL) and human non-Hodgkin lymphoma (NHL),” said Brian Flesner, DVM, MS, DACVIM (Oncology), the primary investigator of the study. “DLBCL is the most common form of canine lymphoma and mirrors NHL, which is the second fastest growing cancer in terms of human mortality. With the high prevalence and increasing mortality rate of lymphoma in both species, research efforts are moving in parallel to improve outcome. Particularly, gene modification therapies are being investigated to result in better responses.
“Our study will enroll client-owned dogs diagnosed with stage three and four DLBCL in groups of three dogs to receive pre-conditioning demethylating agents prior to cytotoxic chemotherapy, single agent doxorubicin. Dogs will be randomized to receive one of the demethylating agents, followed by three standard doses of doxorubicin administered every three weeks,” he explained.
For questions about this study or other ongoing clinical trials at MU, contact our clinical trials doctors or the Oncology Service at 573-882-7821. Prospective participants can also contact Flesner at flesnerb@missouri.edu.
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