Understanding Methotrexate Dosing, Pharmacokinetics, and Toxicities for Burkitt Lymphoma in Malawi

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ABSTRACT This application is for a Fogarty International Center K01 International Research Scientist Development Award for Dr. Katherine Westmoreland, MD, a pediatric hematologist-oncologist at the University of North Carolina (UNC). The award will be based at the longstanding UNC clinical research collaboration in Lilongwe, Malawi, where Dr. Westmoreland has previously lived and worked as a clinical and research fellow. Dr. Westmoreland is in the formative stages of her research career and aims to establish herself as an independent global health investigator in the area of cancer clinical trials for children and adolescents and young adults (AYA). The proposal is specifically focused on Burkitt Lymphoma (BL), the commonest cancer among children and AYA in SSA for which survival is dismal compared to resource-rich settings. To inform the design of future large-scale regional clinical trials to optimize BL treatment for AYA throughout SSA, Dr. Westmoreland proposes to conduct mentored research that will implement a methotrexate dose escalation pilot clinical trial to determine the maximum tolerated dose for this key medicine in international BL treatment protocols (Aim 1); develop a population pharmacokinetic model for methotrexate (Aim 2); and translate, validate, and implement a patient- reported outcomes (PRO) instrument in Malawi for a more comprehensive toxicity assessment (Aim 3). This award will also provide Dr. Westmoreland with support necessary to achieve the following career development goals: 1) obtain formal training in clinical trial design and implementation in SSA; 2) advance her training in clinical pharmacology; 3) learn qualitative and quantitative methods to translate and apply PRO measures for research in SSA; 4) acquire advanced skills in biostatistics; 5) develop expertise in AYA oncology in SSA; and 6) improve grant writing and scientific presentation skills. To achieve these goals Dr. Westmoreland has assembled a highly accomplished core mentorship team comprised of: her primary Malawi mentor, Satish Gopal, MD, MPH, an expert in global oncology and cancer clinical/translational research in SSA; her primary United States mentor, Daniel Gonzalez, PharmD, PhD, a leader in pediatric population pharmacokinetics; and her core mentor Bryce Reeve, PhD, an international expert in PRO methodology. All are NIH-funded investigators with a track record of mentoring junior faculty toward independence. The proposed research and career development plans outlined in this proposal will accelerate Dr. Westmoreland’s global pediatric oncology research career, and form the basis for a future R01 application to lead a multicenter clinical trial to optimize BL treatment for AYA across SSA.