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: 10018127
• 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/10018127
• 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; Herpesviridae Infections; High Prevalence; Hodgkin Disease; Hospitals; Human Herpesvirus 8; Incidence; Income; Inflammation; International; K-Series Research Career Programs; Kaposi Sarcoma; Knowledge; Life; Lymphatic Diseases; 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; Risk; 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; markov model; meetings; microcosting; mortality; multidisciplinary; phase 2 study; prevent; primary outcome; programs; relapse prediction; rituximab; safety testing; secondary outcome; skills; 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.

项目总结/文摘