Preclinical investigation of CC-90009 in models of acute myleoid leukemia
Overall 5-year survival for patients diagnosed with acute myeloid leukemia (AML) is typically between 20-30%. This dismal prognosis highlights the urgent demand for novel therapeutic alternatives. The immunomodulatory drug thalidomide and its derivatives, lenalidomide and pomalidomide, have been successfully repurposed for the treatment of cancer. Furthermore, these compounds have exhibited significant potential for use in the treatment of AML. CC-90009 is a novel thalidomide derivative indicated to efficiently and preferentially target leukemic cells. To fully understand the compounds anti-leukemic potential comprehensive preclinical testing will be performed in multiple mouse xenograft models of human AML. The application of optical imaging modalities utilizing luminescent reporters (luciferase) will enable careful evaluation of disease progression and drug efficacy. Dose finding and schedule optimization studies coupled to pharmacokintetic and biomarker assays will enable dosing of mice that is well tolerated and non toxic yet enables suffiecient biological response. Furthermore combination studies will clinically relevant agents will explore the potential for amplifying the effect of CC-90009.
650 mice will be used over 5 multi-component studies.
In preparation for this study we have performed exhaustive in-vitro studies to determine which cell lines and disease characteristics will be relevant for assessing the drugs under investigation. These studies have significantly reduced the number of variables needed to be examined. To ensure the results are statistically significant, the number of animals and groups in each experiment is sufficiently high to provide definitive results. Similarly size and selection of the groups should avoid the need for repeat experiments. Finally in-vitro testing and pilot studies have determined specific biomarkers for analysis meaning less material is required and fewer animals dedicated to pharmacodynamic studies.
In totality, these studies will generate a detailed evaluation of the therapeutic potential of CC-90009 in peclinical models of AML. The primary goal of the project is to generate comprehnsive preclinical data that can be translated to effective clinical practice for the benefit of AML patients.
650 mice will be used over 5 multi-component studies.
In preparation for this study we have performed exhaustive in-vitro studies to determine which cell lines and disease characteristics will be relevant for assessing the drugs under investigation. These studies have significantly reduced the number of variables needed to be examined. To ensure the results are statistically significant, the number of animals and groups in each experiment is sufficiently high to provide definitive results. Similarly size and selection of the groups should avoid the need for repeat experiments. Finally in-vitro testing and pilot studies have determined specific biomarkers for analysis meaning less material is required and fewer animals dedicated to pharmacodynamic studies.
In totality, these studies will generate a detailed evaluation of the therapeutic potential of CC-90009 in peclinical models of AML. The primary goal of the project is to generate comprehnsive preclinical data that can be translated to effective clinical practice for the benefit of AML patients.