Evaluation of Efficacy and Mechs of Topical Thalidomide

这项随机对照临床试验的目的是通过测试一种新型局部肿瘤坏死因子α（TNF-α）调节剂沙利度胺与安慰剂对慢性移植物抗宿主病（cGVHD）相关口腔炎的影响，阐明炎症在这种口腔疾病中的作用。本研究的具体目的如下：1）评估局部沙利度胺治疗cGVHD相关口腔炎的临床疗效; 2）评估局部沙利度胺治疗cGVHD相关口腔炎的安全性和耐受性;和3）使用局部应用的沙利度胺作为药理学工具检查炎症在cGVHD相关口腔炎中的作用。我们的总体假设是，细胞因子TNF-α通过局部炎症反应在cGVHD相关性口腔炎的发病机制中起主要作用，局部应用假定的TNF-α调节剂沙利度胺可以改变局部炎症反应。该研究计划测试局部沙利度胺与安慰剂在糊剂制剂（N = 66）和漱口剂制剂（N = 66）中的有效性。入选标准包括年龄在18岁至80岁之间的患者，其具有经手术活检结果证实的口腔cGVHD诊断。 本研究的数据和安全性监查计划已获得NINR数据和安全性监查委员会的批准。招募计划于2006年12月开始，等待FDA批准外用沙利度胺凝胶。除了由Richard查尔兹，MD，国家心肺和血液研究所副研究员提供的患者人群外，cGVHD患者将通过国家癌症研究所每周赞助的cGVHD诊所在临床中心，国立卫生研究院（NIH），以及通过国家癌症研究所赞助的cGVHD自然史方案“决定cGVHD患者结局的临床和生物学因素的前瞻性评估”（04-C-0281）。局部沙利度胺由NIH临床中心药物开发服务处制备。

The purpose of this randomized controlled clinical trial is to elucidate the role of inflammation in chronic graft-versus-host-disease (cGVHD)-related stomatitis by testing the effects of a novel topical tumor necrosis factor alpha (TNF-alpha) modulator, thalidomide, versus placebo for this oral condition. The specific aims of this study are the following: 1) to assess the clinical efficacy of topical thalidomide for treatment of cGVHD-related stomatitis; 2) to assess the safety and tolerability of topical thalidomide for the treatment of cGVHD-related stomatitis; and 3) to examine the role of inflammation in cGVHD related stomatitis using topically applied thalidomide as a pharmacologic tool. Our overall hypothesis is that the cytokine TNF-alpha plays a major role in the pathogenesis of cGVHD-related stomatitis via the local inflammatory response, which is modified by the topical application of the putative TNF-alpha modulator, thalidomide. The study is planned to test the effectiveness of topical thalidomide versus placebo in a paste formulation (N = 66), and also in a mouthwash formulation (N = 66). Inclusion criteria include patients between the ages of 18 and 80 who have a diagnosis of oral cGVHD as confirmed by surgical biopsy results. The data and safety monitoring plan for the study has been approved by the NINR Data and Safety Monitoring Board. Recruitment is planned to begin in December 2006 pending FDA approval of the topical thalidomide gel. In addition to the patient population provided by Richard Childs, MD, Associate Investigator, National Heart, Lung, and Blood Institute, cGVHD patients will be referred through the weekly National Cancer Institute sponsored cGVHD Clinic at the Clinical Center, National Institutes of Health (NIH), as well as through the National Cancer Institute-sponsored cGVHD natural history protocol "Prospective Assessment of Clinical and Biological Factors Determining Outcomes in Patients with cGVHD" (04-C-0281). Topical thalidomide is prepared by the Pharmaceutical Development Service, Clinical Center, NIH.