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

摘要 此应用程序是一个福格蒂国际中心K 01国际研究科学家发展奖 凯瑟琳威斯特摩兰博士，医学博士，儿科血液肿瘤学家在北卡罗来纳州大学 （二）。该奖项将基于马拉维利隆圭的长期临床研究合作， Westmoreland博士曾在那里生活和工作，担任临床和研究员。威斯特摩兰博士 她正处于研究生涯的形成阶段，目标是成为一个独立的全球健康 儿童、青少年和年轻人（AYA）癌症临床试验领域的研究者。的 该提案特别关注伯基特淋巴瘤（BL），这是儿童和青少年中最常见的癌症。 与资源丰富的环境相比，撒哈拉以南非洲的生存状况令人沮丧。为未来大型建筑的设计提供参考 区域临床试验，以优化整个SSA的BL治疗AYA，Westmoreland博士建议， 进行指导研究，实施甲氨蝶呤剂量递增试点临床试验，以确定 国际BL治疗方案中这种关键药物的最大耐受剂量（目标1）;制定 甲氨蝶呤的群体药代动力学模型（目标2）;并翻译，验证和实施患者- （b）在马拉维使用报告结果（PRO）工具进行更全面的毒性评估（目标3）。这 该奖项还将为Westmoreland博士提供必要的支持，以实现以下职业生涯 发展目标：1）获得临床试验设计和SSA实施的正式培训; 2）推进 她在临床药理学方面的培训; 3）学习定性和定量方法来翻译和应用PRO SSA研究措施; 4）获得生物统计学的高级技能; 5）发展AYA肿瘤学的专业知识 在SSA;和6）提高赠款写作和科学演示技巧。为了实现这些目标，博士。 Westmoreland组建了一个非常成功的核心导师团队，包括： 马拉维导师Satish Gopal，医学博士，公共卫生硕士，全球肿瘤学和癌症临床/转化研究专家 在SSA;她的主要美国导师，丹尼尔冈萨雷斯，药学博士，博士，在儿科人口的领导者 她的核心导师Bryce Reeve博士是PRO方法学的国际专家。所有 是NIH资助的研究人员，有指导初级教师走向独立的记录。的 本提案中概述的拟议研究和职业发展计划将加速Westmoreland博士的 全球儿科肿瘤学研究事业，并形成未来R 01申请的基础，以领导多中心 临床试验，以优化整个SSA的AYA BL治疗。

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.