Optimizing Stem Cell Transplant for Cancer

描述(申请人提供)：帕玛拉·雅各布森，药学博士，明尼苏达大学实验和临床药理学系助理教授。她在造血干细胞移植(HSCT)方面有9年的临床经验，现在希望将自己的职业重点转向临床研究。她的长期职业目标是成为一名专注于HSCT临床药理学的独立研究员。她的直接目标是接受研究培训，为自己成为一名独立资助的调查员做准备。她建议在导师的指导下进行临床研究并完成临床研究硕士课程。明尼苏达大学是世界上最古老和最大的基于学术的HSCT项目之一，是一流的药学学院和公共卫生学院，并具备支持候选人的良好条件。研究计划将集中在临床试验设计、生物统计学、伦理学、药代动力学和药效学。申请人的研究将探索免疫抑制剂霉酚酸酯的药代动力学，以及非清髓性异基因造血干细胞移植的药代动力学和临床结果之间的关系。毒性较低的含有霉酚酸酯的“非清髓性”制剂方案正在研究中。这些方案使用标准的固定剂量的霉酚酸酯，并与不同的免疫抑制和结果相关。我们假设结果的可变性与霉酚酸酯药代动力学的差异有关。具体目的I将评估霉酚酸酯药代动力学措施与临床终点之间的关系。SPARTICAL AIM II将评估移植前霉酚酸酯的药代动力学，以确定患者间的变异性，并确定与其变异性相关的协变量。特殊目标III将评估移植后的药代动力学，以确定患者内部的变异性，并确定与变异性相关的移植围手术期事件。我们预计监测霉酚酸酯的浓度和个体化给药是必要的。这项研究的长期目标是降低非清髓性HSCT后移植物对宿主疾病的发生率、移植物衰竭、毒性和提高存活率。总体目标是为申请人提供作为临床癌症研究人员的正式和全面的培训。

DESCRIPTION (provided by applicant): Pamala Jacobson, Pharm.D. is an Assistant Professor in the Department of Experimental and Clinical Pharmacology at the University of Minnesota (MN). She has 9 years of clinical experience in hematopoietic stem cell transplantation (HSCT) and now wishes to change her career focus to clinical research. Her long-termcareer goal is to become an independent investigator focusing on clinical pharmacology in HSCT. Her immediate goal is, to receive research training to prepare herself as an independently funded investigator. She proposes to conduct mentored clinical research under her mentors and complete the Clinical Research Masters Program, University of MN, The University of MN is home to one of the oldest and largest academically based HSCT programs in the world, a top-ranked College of Pharmacy and School of Public Health, and is well equipped to support the candidate. The program of study will focus on clinical trial design, biostatistics, ethics, pharmacokinetics and pharmacodynamics. The applicant's research will explore the pharmacokinetics of the immunosuppressant, mycophenolate, and the relationships between pharmacokinetics and clinical outcomes in nonmyeloablative allogeneic HSCT. Less toxic "nonmyeloablative" preparative regimens, containing mycophenolate, are under investigation. These regimens use a standard, fixed dose of mycophenolate and are associated with variable immunosuppression and outcomes. We hypothesize that the variability in outcomes is related to differences in mycophenolate pharmacokinetics. Specific Aim I will evaluate the relationships between mycophenolate pharmacokinetic measures and clinical endpoints. Specific Aim II will assess pretransplant mycophenolate pharmacokinetics to determine inter-patient variability and identify covariates associated with their variability. Specific Aim III will assess posttransplant pharmacokinetics to determine intra-patient variability and identify peritransplant events associated with variability. We anticipate that monitoring of mycophenolate concentrations and individualized dosing is warranted. The long-term goal of this research is to reduce the rates of graft vs. host disease, graft failure, toxicity and improve survival following nonmyeloablative HSCT. The overall goal is to provide the applicant with formal and comprehensive training as a clinical cancer investigator.