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 (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 study will begin to accrue subjects following the approval of the protocol data and safety monitoring plan by the Data and Safety Monitoring Board, which convened in August, 2005. In addition to the patient population provided by Richard Childs, MD, Associate Investigator, National Heart, Lung, and Blood Institute, cGVHD patients may 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. The IRB was informed on September 20, 2004 that the protocol was transferred from the National Insitute of Dental and Craniofacial Research to the National Institute of Nursing Research.
