Planning a phase I study of minor salivary gland derived autologous MSCs for prevention of long-term radiation induced xerostomia

项目摘要 口干是头颈部癌症患者放射治疗的一个重要副作用。几个因素 有助于口干。唾液分泌减少称为唾液过少。质量和功能较差 唾液被称为唾液功能障碍。这些因素共同导致口腔干燥症，或患者经历的 只是口干。口腔干燥症会导致蛀牙、感染、说话困难、吞咽障碍、 营养不良，并对生活质量产生重大负面影响。医生建议病人用力吮吸 糖果，口香糖，使用唾液替代品，和/或随身携带水瓶。这些都不是 特别有效。我们的长期目标是防止发展长期辐射引起的干旱 口腔改善头颈部癌症患者的生活质量。我们力求通过以下方式实现这一目标： 提供了令人信服的证据，证明创新的细胞疗法可以安全，显著地预防 长期唾液腺功能障碍的发展。处理这个项目的调查小组是独一无二的， 适合完成工作。成功将直接导致下一阶段的临床试验。我们有 在照顾头颈部癌症患者方面的专业知识，开发小唾液腺衍生的间充质细胞， 基质细胞（MSC）作为细胞疗法，并研究唾液功能。本报告的总体目标 申请是计划和准备1期试验，以测试IFN-g预许可的安全性和耐受性 小唾液腺来源的间充质干细胞预防头颈部肿瘤放射性口干症的实验研究 患者为了实现我们的目标，我们提出了一个里程碑式的项目，我们将与 NIH和FDA将完成1期安全性和耐受性研究的研究设计，完成临床试验 方案，并提交目标1中的监管文件。在目标2中，我们将完成所有必要的里程碑， 启动拟议的临床试验，包括安全系统、数据系统、研究中心工作人员和设施准备 以确保计划中的临床试验顺利进行。

Project Abstract Dry mouth is a significant side-effect of radiation therapy for head and neck cancer patients. Several factors contribute to dry mouth. Decreased production of saliva is called hyposalivation. Poor quality and function of saliva is called salivary dysfunction. Together, these cause xerostomia, or what a patient experiences as simply dry mouth. Xerostomia can lead to tooth decay, infections, difficulty speaking, impaired swallowing, poor nutrition, and has a significant negative effect on quality of life. Doctors recommend that patients suck on hard candy, chew gum, use saliva substitutes, and/or carry a water bottle with them at all times. None of these are particularly effective. Our long-term goal is to prevent the development of long-term radiation-induced dry mouth to improve the quality of life for patients with head and neck cancer. We seek to achieve this goal by providing convincing evidence that innovative cellular therapies can safely and significantly prevent the development of long-term salivary gland dysfunction. The team of investigators tackling this project is uniquely suited to complete the work. Success would lead directly to the next phase of clinical testing. We have expertise in caring for head and neck cancer patients, developing minor salivary gland derived mesenchymal stromal cells (MSCs) as cellular therapies, and studying salivary function. The overall objective of this application is to plan and prepare for a Phase 1 trial to test the safety and tolerability of IFN-g pre-licensed minor salivary gland derived MSCs for prevention of radiation-induced xerostomia in head and neck cancer patients. To achieve our goals, we propose a milestone-based project in which we will work closely with the NIH and FDA to finalize study design for a Phase 1 safety and tolerability study, complete the clinical trial protocol, and submit regulatory documents in Aim 1. In Aim 2, we will complete all necessary milestones to activate the proposed clinical trial including safety systems, data systems, and site staff and facility preparation to ensure a smooth opening to the planned clinical trial.