• Progress in oral ulcer healing. [ Designated as safety issue: Yes ]
  

Drug: Thalidomide
N/A
Drug: Thalidomide Gel
N/A

Oncology patients undergoing allogeneic bone marrow/peripheral blood stem cell transplant (HSCT) frequently experience an allo-immune condition termed graft-versus-host-disease (GVHD). The pathogenesis of GVHD derives from an immune attack mediated by donor T-cells recognizing antigens expressed on normal tissues of the patient. This condition occurs in ABMT rather than autologous BMT because of disparities in minor histocompability antigens between donor and recipient, inherited independently of HLA genes. GVHD may be conceptualized as a cytokine storm stemming from an outpouring of endogenous cytokines resulting in many tissue effects. Oral chronic GVHD (cGVHD), which is classically diagnosed as a late complication of ABMT occurring more than 100 days post transplant, presents with tissue atrophy and erythema, lichenoid changes (hyperkeratotic striae, patches, plaques, and papules) and pseudomembranous ulcerations typically occurring on the buccal and labial mucosa and the lateral tongue, mucoceles due to inflammation of minor salivary glands, and xerostomia. The ulcerative phase often leads to a cascade of negative sequelae including oropharyngeal pain, critical treatment alterations or cessation, diminished capacity for food intake, and decreased quality of life. We hypothesize that the mechanisms of tissue injury occurring at the mucosal level leading to cGVHD-related stomatitis are similar to other types of stomatitis, such as chemotherapy-related and aphthous stomatitis, and are therefore amenable to treatment with anti-inflammatory strategies.

Optimal treatment strategies for cGVHD-related ulcerative stomatitis and related oropharyngeal pain have not been established. Therefore, there is a critical need to examine the pathogenesis of and to evaluate interventions for cGVHD-related ulcerative stomatitis and related acute oropharyngeal pain in the randomized controlled clinical trial setting to both advance the science of cancer treatment-related oral complications and to improve patient care. Therefore, the purpose of this study is to elucidate the role of inflammation in GVHD-related ulcerative stomatitis by testing the efficacy of topical thalidomide on the resolution of cGVHD-related stomatitis and related oropharyngeal pain. The actions of thalidomide, which include inhibition of the release of tumor necrosis factor-alpha (TNF-alpha) and resultant alteration of the inflammatory cascade, may provide insight into the role of local mucosal inflammation in cGVHD-related stomatitis.

• INCLUSION CRITERIA:

Participating in HSCT or cGVHD protocols and willing to participate in this study concurrently;

Diagnosed with oral cGVHD stomatitis confirmed by surgical biopsy results;

Oral ulceration present

Able to understand and sign protocol informed consent;

Ages 18 to 80 years of age.

EXCLUSION CRITERIA:

Pregnant or lactating females;

For the proof of concept study, females who are not surgically sterilized by means of hysterectomy or tubal ligation;

For the main study, females of childbearing potential who do not agree to the use of two arms of highly effective contraception for at least four weeks prior, during, and for four weeks following the last dose of study drug;

Sexually active males who do not agree to the use of a latex condom while receiving study drug and for four weeks following the last dose of study drug;

Unwilling to follow precautions for use of thalidomide;

Unable to demonstrate appropriate use of study medication;

Concurrent use of non-protocol-related medications confounding assessment of the inflammatory response (antihistamines, non-steroidal anti-inflammatory drugs);

Allergic reaction to thalidomide;

Pre-existing oral infection, which might maximize the possibility of an infection or sepsis contributing to a drug-related adverse event;

Unwilling to forego concurrent treatment for mucosal lesions and/or related oral pain (including topical steroids, viscous lidocaine, topical anti-fungals);

Requiring addition of new systemic therapy including thalidomide, steroids, or radiation therapy;

Use of sedatives (including CNS depressants);

Absolute neutrophil count (ANC) less than 750/mm(3)