Biomarkers and Targeted Therapy of Bronchiolitis Obliterans

闭塞性细支气管炎的生物标志物和靶向治疗

• 批准号: 8327077
• 负责人: JASON W CHIEN
• 金额: $ 25.03万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8327077
• 关键词: Acute; Acute Graft Versus Host Disease; Alloantigen; Allogenic; Azithromycin; Biological Markers; Blood; Bronchiolitis Obliterans; Cell Transplantation; Cell Transplants; Clinical; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Clinical assessments; Complement; Data; Disease; Ensure; FDA approved; Functional disorder; Funding; Future; Goals; Hematopoietic; Immune; Immune system; Intention; Knowledge; Laboratories; Laboratory Study; Liquid substance; Lung; Mediating; Pharmaceutical Preparations; Phase; Pilot Projects; Population; Procedures; Pulmonary function tests; Rare Diseases; Resources; Syndrome; T memory cell; Testing; Time; Translational Research; Transplantation; United States National Institutes of Health; Work; alefacept; chronic graft versus host disease; clinical application; data management; flexibility; fluticasone; member; montelukast; novel therapeutics; programs; quality assurance; research study; response

The goal of the Pilot/Demonstration Progam is to conduct early phase research studies what will advance our knowledge about immune mediated disorders after allogeneic hematopoietic cell transplantation (HCT). We propose three pilot studies focused on clinical/translational research. Additional pilot studies may be funded or may replace these studies, depending on evolving knowledge in the field. Pilot 1 focuses on bronchiolitis obliterans syndrome (BOS) and proposes a small (N=40) clinical trial testing a treatment approach targeting the innate and adaptive immune system using a combination of fluticasone, azithromycin and montelukast. All three agents are relatively nontoxic FDA-approved medications with preliminary data suggesting benefit in both the lung transplant and allogeneic HCT BOS settings. Biomarker studies from bronchoalveolar fluid and blood will complement clinical assessment of response using serial pulmonary function tests. Two other pilot studies currently planned for the later half of the funding period focus on the pathophysiology and treatment of late acute graft versus host disease (GVHD). One is a clinical trial potentially testing alefacept, an agent targeted to memory T cells. The other is a laboratory study to evaluate whether effector or memory T cell populations specific for recipient alloantigens are associated with late acute and classic chronic GVHD. Selection of pilot projects and management of the Pilot/Demonstration Program is the responsibility of the Rare Diseases Clinical Research Consortium (RDCRC) PI with input from other members of Consortium. Criteria for pilot project selection emphasize scientific potential and integration/synergy with other RDCRC initiatives. Mechanisms for quality assurance, data management, Data Safety Monitoring Board oversight and interactions with the entire Consortium will mirror the procedures established for the Projects. We will work closely with NIH program officers to ensure that the Pilot Program is fulfilling the funding intention.

飞行员/示范进程的目的是进行早期研究研究 我们对同种异性造血细胞移植（HCT）后免疫介导的疾病的了解。 我们提出了三项针对临床/转化研究的试点研究。其他试点研究可能是 根据现场不断发展的知识，资助或可能取代这些研究。飞行员1专注于 支气管炎闭塞综合征（BOS），并提出了一项小（n = 40）的临床试验测试 使用氟替卡酮的组合，靶向先天和适应性免疫系统的方法 和Montelukast。所有三个药物都是相对无毒的FDA批准的药物，并具有初步数据 暗示在肺移植和同种异体HCT BOS设置中均受益。生物标志物研究 支气管肺泡液和血液将使用串行肺部对反应的临床评估进行补充 功能测试。目前，其他两项试点研究计划在资金期间的后期重点关注 急性移植物与宿主病（GVHD）的病理生理学和治疗。一个是临床试验 潜在测试AlefacePT，一种针对内存T细胞的代理。另一个是一项实验室研究 效应子还是记忆T细胞种群，适用于同种植物的受体群体与迟到有关 急性和经典慢性GVHD。 选择试点项目和试点/示范计划的管理是 罕见的疾病临床研究联盟（RDCRC）PI和联盟其他成员的投入。 试点项目选择的标准强调了与其他RDCRC的科学潜力和整合/协同作用 倡议。质量保证，数据管理，数据安全监控委员会监督机制 与整个财团的互动将反映为项目建立的程序。我们将 与NIH计划官员紧密合作，以确保试点计划符合资金意愿。