Safety, efficacy, and cost-effectiveness of rituximab for multicentric Castleman disease in Malawi

利妥昔单抗治疗马拉维多中心 Castleman 病的安全性、有效性和成本效益

• 批准号: 10189741
• 负责人: Matthew Scott Painschab
• 金额: $ 14.39万
• 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: 2019-09-16 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189741
• 关键词: AIDS related cancer; Address; Adverse event; Africa South of the Sahara; Age; Award; B-Lymphocytes; Biological Markers; Biometry; C-reactive protein; CD4 Lymphocyte Count; Capital; Cessation of life; Cities; Clinical Practice Guideline; Clinical Research; Clinical Trials; Clinical Trials Design; Common Terminology Criteria for Adverse Events; Cost Effectiveness Analysis; Country; Cox Proportional Hazards Models; Data; Decision Modeling; Development; Disease; Disease remission; Disease-Free Survival; Doctor of Philosophy; Dose; Enrollment; Environment; Etoposide; Frequencies; Future; Goals; HIV; HIV Infections; Health system; Hemoglobin; Herpesviridae Infections; High Prevalence; Hodgkin Disease; Hospitals; Human Herpesvirus 8; Incidence; Income; International; K-Series Research Career Programs; Knowledge; Life; Lymphoproliferative Disorders; MS4A1 gene; Malawi; Malignant Neoplasms; Medicine; Mentored Research Scientist Development Award; Mentors; Mentorship; Modeling; Monoclonal Antibodies; Monoclonal Antibody CD20; Morbidity - disease rate; Multicentric Angiofollicular Lymphoid Hyperplasia; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Outcome; Patient-Focused Outcomes; Patients; Phase; Phase II Clinical Trials; Plasma; Prevalence; Prospective Studies; Prospective cohort; Proteins; Publishing; Relapse; Reporting; Research; Research Personnel; Research Support; Resources; Safety; Sampling; Seroprevalences; Symptoms; Time; Toxic effect; Training; United States National Institutes of Health; Weight; Work; anti-CD20; antiretroviral therapy; arm; base; burden of illness; cancer care; career; chemotherapy; comorbidity; comparative cost effectiveness; cost; cost effective; cost effectiveness; cost-effectiveness evaluation; disability-adjusted life years; disorder control; efficacy trial; experience; global health; high risk; improved; insight; international center; low and middle-income countries; low income country; lymphadenopathy; markov model; meetings; microcosting; mortality; multidisciplinary; phase 2 study; prevent; primary outcome; programs; relapse prediction; risk stratification; rituximab; safety testing; secondary outcome; skills; systemic inflammatory response; willingness to pay

PROJECT SUMMARY/ABSTRACT Dr. Matthew Painschab is applying for a Fogarty International Center K01 International Research Scientist Development Award. Dr. Painschab has shown promise as a young investigator in global health but needs further training to achieve research independence. This award will provide him with five years of mentored research time and he will spend >75% of the award period based at UNC Project Malawi and Kamuzu Central Hospital in Lilongwe, the capital city of Malawi. His goal is to become an expert and independent researcher in clinical trials and cost-effectiveness of cancer care in sub-Saharan Africa (SSA), specifically, multicentric Castleman’s disease and other Kaposi sarcoma-associated herpesvirus (KSHV)-related diseases. His primary mentors for this award are Dr. Satish Gopal, MD, MPH (Primary LMIC-based Mentor, cancer clinical research in SSA) and Dr. Stephanie Wheeler, PhD, MPH (Primary US-based Mentor, decision modeling and cost- effectiveness analysis). Through a combination of mentorship, coursework, and practical experience, Dr. Painschab proposes to accomplish the following training objectives: 1) advanced training in clinical trials design and implementation; 2) advanced training in microcosting and cost-effectiveness modeling; and 3) advanced training in KSHV pathobiology. This training plan will support a rigorous research plan in MCD, a life- threatening lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy that is strongly associated with KSHV and human immunodeficiency virus (HIV). This disease is much more prevalent in SSA because of a much higher prevalence of KSHV and HIV infections. Chemotherapy is rarely, if ever, effective in preventing morbidity and mortality from this disease. However, in small studies in high income countries, rituximab, a monoclonal antibody against CD20, a protein commonly found on B cells, has been effective in inducing long-term remissions. In this application, we propose testing the safety and efficacy of rituximab-based treatment for MCD (AIM 1) in a single arm, phase II study in Malawi. We will also conduct a comprehensive microcosting study of treatment of MCD in Malawi and use outcomes from AIM 1 to establish a Markov model (AIM 2) that we will use to analyze the cost-effectiveness of rituximab-based therapy. This research will establish a unique prospective cohort of MCD patients and samples that can be leveraged for future independent research awards to better understand this emerging HIV-associated comorbidity and improve patient outcomes in both SSA and high-income countries.

项目概要/摘要 Matthew Painschab博士正在申请福格蒂国际中心K01国际研究科学家 发展奖。 Painschab 博士作为一名年轻的全球卫生研究者已展现出潜力，但仍需要 进一步培训以实现研究独立性。该奖项将为他提供五年的指导 他将在北卡罗来纳大学马拉维项目和 Kamuzu Central 度过超过 75% 的研究时间 马拉维首都利隆圭的医院。他的目标是成为一名专家和独立研究员 撒哈拉以南非洲 (SSA) 癌症治疗的临床试验和成本效益，特别是多中心 卡斯尔曼氏病和其他卡波西肉瘤相关疱疹病毒 (KSHV) 相关疾病。他的小学 该奖项的导师是 Satish Gopal 博士，医学博士、公共卫生硕士（中低收入国家初级导师，癌症临床研究 SSA 博士）和 Stephanie Wheeler 博士，博士，公共卫生硕士（美国主要导师，决策建模和成本- 效果分析）。通过指导、课程作业和实践经验的结合，博士。 Painschab建议完成以下培训目标：1）临床试验高级培训 设计和实施； 2）微观成本计算和成本效益建模的高级培训；和 3) KSHV 病理学高级培训。该培训计划将支持 MCD 的严格研究计划，MCD 是一项终身研究 以全身炎症和淋巴结肿大为特征的威胁性淋巴组织增生性疾病 与 KSHV 和人类免疫缺陷病毒 (HIV) 密切相关。这种病比较普遍 在 SSA，因为 KSHV 和 HIV 感染的患病率要高得多。化疗很少（如果有的话） 有效预防这种疾病的发病和死亡。然而，在高收入人群的小型研究中 利妥昔单抗（rituximab）是一种抗 CD20（B 细胞上常见的蛋白质）的单克隆抗体。 有效诱导长期缓解。在此应用中，我们建议测试以下药物的安全性和有效性： 在马拉维进行的单臂 II 期研究中基于利妥昔单抗的 MCD 治疗 (AIM 1)。我们还将举办一次 对马拉维 MCD 治疗进行全面微观成本研究，并利用 AIM 1 的结果建立 我们将使用马尔可夫模型 (AIM 2) 来分析基于利妥昔单抗的治疗的成本效益。这 研究将建立一个独特的 MCD 患者前瞻性队列和样本，可用于 未来的独立研究奖项将更好地了解这种新出现的艾滋病毒相关合并症， 改善 SSA 和高收入国家的患者治疗效果。