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: 10397542
• 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/10397542
• 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; Fogarty International Center; 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; 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.

摘要