Non-Hodgkin's Lymphoma (NHL) represents 4% of all cancer diagnosed in the U.S., and as many as 50% of patients will relapse within 2 years of diagnosis and treatment. The current standard of care ischemotherapy. For Diffuse Large B cell Lymphoma subtype (DLBCL) CHOP (cyclophosphamide-doxorubicin-vincristine-prednisone) is given in combination with an anti-CD20 monoclonal antibody, such asrituximab (R-CHOP). Unfortunately, chemotherapy requires numerous treatment cycles with challenging sideeffects and does not completely remove the cancerous lymphocytes, as indicated by the frequency of relapse.A drug that could reduce the lymphoma population and essentially increase the potency of the chemotherapyregimen (fewer lymphoma cells to the chemotherapy concentration) would have the potential to be synergisticas a treatment strategy. AVM0703, a proprietary formulation of high concentration dexamethasonedeveloped by AVM Biotechnology, has been shown to control NHL growth in murine models. It also safelyreduces lymphocytes following a single very high dose via one-hour infusion, in both pre-clinical and clinicalsettings. AVM0703 is currently the subject of a US-based clinical study in no-option, relapsed/refractory NHLpatients and is distinguished from other investigative drugs in this "terminal no-option' patient population byits absence of safety concerns with patients reporting feeling great, regaining appetite and energy, anddurable response recorded. The goal of this project is to validate the combination of AVM0703 and standardDLBCL chemotherapy R-CHOP. This approach is expected to increase complete response rates andpotentially reduce the required number of chemotherapy cycles, providing a more tolerable therapeutic optionfor newly diagnosed NHL patients. The feasibility of this approach will be validated in Phase I with thefollowing aims: Aim 1) Evaluate the ability of AVM0703 in combination with R-CHOP to reduce R-CHOPcycles in an aggressive, immune-resistant murine B cell NHL model. Aim 2) Assessment of AVM0703combination therapy with reduced dose R-CHOP to enhance outcomes in elderly patients. The Phase IIproject will further focus on efficacy studies, and a small clinical trial with newly diagnosed NHL patients toevaluate the effects of this novel therapeutic treatment approach.
Public Health Relevance Statement: PROJECT NARRATIVE
While the anti-CD20 antibody Rituxan in combination with standard of care (SOC) chemotherapy
administered typically in six repeat cycles elicits high response rates in Non-Hodgkin's Lymphoma (NHL),
relapse rates are high and long-term toxicities problematic, which include secondary cancers caused by the
treatment itself, as well as substantial neuro- and cardiac toxicities. AVM0703, as a stand-alone in terminal
no-option NHL patients, has had few side-effects, patient's report "feeling great", and durable response has
been recorded. AVM0703 in combination with NHL SOC such as R-CHOP could reduce relapse rates and
even potentially limit the total number of chemotherapy cycles required for complete response, significantly
impacting patient's short and long-term quality of life.
Project Terms: | <14-Hydroxydaunomycin><1, 2-Dehydrocortisone> | | 