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: 7978971
• 负责人: JASON W CHIEN
• 金额: $ 26.23万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7978971
• 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.

试点/示范计划的目标是进行早期阶段的研究，以推动未来的发展 我们对异基因造血细胞移植（HCT）后免疫介导疾病的了解。 我们提出了三项专注于临床/转化研究的试点研究。额外的试点研究可能是 资助或可能取代这些研究，具体取决于该领域知识的不断发展。试点 1 重点关注 闭塞性细支气管炎综合征 (BOS) 并提出一项小型 (N=40) 临床试验来测试治疗方法 使用氟替卡松和阿奇霉素组合靶向先天性和适应性免疫系统的方法 和孟鲁司特。所有三种药物都是 FDA 批准的相对无毒的药物，并有初步数据 这表明肺移植和同种异体 HCT BOS 环境都有益处。生物标志物研究来自 支气管肺泡液和血液将补充使用连续肺部反应的临床评估 功能测试。目前计划在资助期后半段进行的另外两项试点研究重点关注 晚期急性移植物抗宿主病（GVHD）的病理生理学和治疗。一是临床试验 可能测试 alefacept，一种针对记忆 T 细胞的药物。另一个是实验室研究来评估 受体同种抗原特异性的效应 T 细胞群或记忆 T 细胞群是否与晚期相关 急性和典型的慢性 GVHD。 试点项目的选择和试点/示范计划的管理由 罕见疾病临床研究联盟 (RDCRC) PI 以及联盟其他成员的意见。 试点项目选择标准强调科学潜力以及与其他 RDCRC 的整合/协同 倡议。质量保证、数据管理、数据安全监察委员会监督机制 与整个联盟的互动将反映为项目制定的程序。我们将 与 NIH 项目官员密切合作，确保试点项目实现资助意向。