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

了解马拉维伯基特淋巴瘤的甲氨蝶呤剂量、药代动力学和毒性

• 批准号: 10153913
• 负责人: Katherine Douglas Westmoreland
• 金额: $ 14.28万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153913
• 关键词: AIDS Malignancy Consortium; Adolescent and Young Adult; Adult; Adverse event; Africa South of the Sahara; Anthracycline; Area; Assessment tool; Award; Biometry; Board Certification; Burkitt Lymphoma; Caring; Centers of Research Excellence; Cessation of life; Child; Childhood; Clinical; Clinical Pharmacology; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Common Terminology Criteria for Adverse Events; Country; Data; Development Plans; Doctor of Pharmacy; Doctor of Philosophy; Dose; Dose-Limiting; Drug Exposure; Drug Kinetics; Effectiveness; Enrollment; Evaluation; Faculty; Fellowship; Funding; Future; Goals; Grant; Growth; Health; Hospitals; Hour; Income; Infrastructure; Infusion procedures; International; Laboratories; Lead; Learning; Longitudinal cohort; Lymphoma; Lymphoproliferative Disorders; Malawi; Malignant Childhood Neoplasm; Malignant Neoplasms; Maximum Tolerated Dose; Measures; Medicine; Mentored Research Scientist Development Award; Mentors; Mentorship; Methodology; Methods; Methotrexate; Monitor; Multi-Institutional Clinical Trial; North Carolina; Oncologist; Oncology; Outcome; Outcome Measure; Patient Outcomes Assessments; Patient Self-Report; Patients; Pediatric Hematologist; Pediatric Hematology; Pediatric Oncology; Pharmaceutical Preparations; Pharmacy Schools; Pharmacy facility; Phase; Physicians; Population; Provider; Public Health Schools; Refractory; Regimen; Relapse; Reporting; Research; Research Personnel; Resources; Sampling; Site; Supportive care; Survival Rate; Time; Toxic effect; Training; Translating; Translational Research; Treatment Protocols; Treatment-related toxicity; United States; United States National Institutes of Health; Universities; Validation; Work; Writing; aged; base; blood product; cancer clinical trial; career; career development; chemotherapy; design; experience; global health; health related quality of life; high risk; improved; instrument; international center; low and middle-income countries; multidisciplinary; pediatric patients; pharmacokinetic model; programs; prospective; ranpirnase; research and development; response; skills; standard of care; treatment optimization; trial design

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.

抽象的 该申请是为Fogarty International Center K01国际研究科学家发展奖 北卡罗来纳大学的儿科血液学家凯瑟琳·韦斯特摩兰博士，医学博士 （UNC）。该奖项将基于马拉维利隆威的长期以来的UNC临床研究合作 Westmoreland博士以前曾住过并担任临床和研究人员。威斯特摩兰博士 处于她研究生涯的形成阶段，旨在将自己确立为独立的全球健康 儿童，青少年和年轻人（AYA）的癌症临床试验领域的研究人员（AYA）。 提案专门针对Burkitt淋巴瘤（BL），这是儿童中最常见的癌症，Aya中的癌症 与资源丰富的设置相比，生存的SSA是惨淡的。告知未来大规模的设计 区域临床试验以优化整个SSA的AYA的BL治疗，Westmoreland博士提议 进行了Mendored研究，该研究将实施MethodyoteDoxate升级试验临床试验以确定 在国际BL治疗方案中，该关键药物的最大耐受剂量（AIM 1）；开发 方法二邻苯二酸的种群药代动力学模型（AIM 2）；并翻译，验证和实施患者 - 马拉维的报告结果（Pro）仪器进行了更全面的毒性评估（AIM 3）。这 奖项还将为Westmoreland博士提供实现以下职业所需的支持 发展目标：1）在SSA中获得临床试验设计和实施方面的正式培训； 2）进步 她在临床药理学方面的培训； 3）学习翻译和应用程序的定性和定量方法 SSA研究措施； 4）获得生物统计学的先进技能； 5）发展AYA肿瘤学专业知识 在SSA； 6）提高赠款写作和科学演示技巧。为了实现这些目标。 威斯特摩兰（Westmoreland Malay Mentor，Satish Gopal，医学博士，MPH，全球肿瘤学和癌症临床/转化研究专家 在SSA；她的主要美国精神，丹尼尔·冈萨雷斯（Daniel Gonzalez） 药代动力学；以及她的核心心理布莱斯·里夫（Bryce Reeve）博士，是Pro方法论的国际专家。全部 是NIH资助的调查员，具有对独立的初级教师的记录。这 该提案中概述的拟议的研究和职业发展计划将加速Westmoreland博士的 全球小儿肿瘤学研究职业，构成了未来R01领导多中心的申请的基础 临床试验以优化SSA跨SSA的AYA的BL治疗。