This study will be conducted in two parts. The first part is a pilot study testing the effects of a thalidomide ointment in patients who have developed oral chronic graft-versus-host-disease (GVHD)-related ulcerative stomatitis following allogeneic bone marrow transplantation (ABMT). Stomatitis is an inflammation of the lining of the throat and mouth that may lead to ulcers and pain in the mouth and throat. GVHD - a condition in which the donor cells see patient's cells as foreign and mount an immune response to them - may be related to increased levels of a substance called TNF-alpha following ABMT. Thalidomide's anti-inflammatory effects may lower TNF-alpha levels and decrease chronic GVHD-related stomatitis and oral pain in these patients.

If this first part of the study is successful, then the second part of the study will be conducted. The second part of this study will test the effects of a thalidomide mouthwash in treating stomatitis in patients who have developed oral chronic graft-versus-host-disease (GVHD)-related stomatitis following allogeneic bone marrow transplantation (ABMT). Applying thalidomide directly to the GVHD-related mouth ulcer in ointment form or to the entire oral cavity by mouthwash form rather than taking it as a pill may reduce the amount of drug that enters the blood stream and cause fewer side effects.

Patients between 18 and 80 years of age who have received an ABMT and developed oral chronic GVHD-related stomatitis as confirmed by surgical biopsy may be eligible for this study. The only eligible female participants for the pilot study will be women who are unable to have children. In the pilot study, participants will be randomly assigned to receive thalidomide ointment or placebo (an ointment with no thalidomide) to use four times a day. In the mouthwash study, participants will be randomly assigned to receive thalidomide mouthwash or placebo (a mouth rinse with no thalidomide) to use four times a day. Participants will also undergo the following procedures before beginning medication, then once a week for 4 weeks, and then approximately 8 weeks after the first visit.

- Interview about current medications and use of alcohol and cigarettes.

- Self-report of mouth and throat pain ratings.

- Dental examination.

- Quality of life questionnaire (The questionnaire is repeated only at week 8 of the study.).

- Mouth photography to measure and record the response to treatment.

- Saliva sampling to look for chemicals, including TNF-alpha.

- Ulcer exudate collected by filter paper to obtain fluid for measuring TNF-alpha levels.

- Gentle swabbing of ulcers to culture for virus, fungus, and bacteria that may be present.

- Small punch biopsy of the area near the ulcer or affected area to check for TNF-alpha (The punch biopsy is repeated only at week 4 of the study.)

- Blood sampling to monitor thalidomide and TNF-alpha levels.

- A urine pregnancy test for women who are able to have children. (The pregnancy test is repeated at weeks 2, 4, and 8.)

Treatment or Intervention	Phase
Drug: Thalidomide	Phase II

Further Study Details: 

Expected Total Enrollment:  132

Oncology patients undergoing allogeneic bone marrow/peripheral blood stem cell transplant (ABMT) 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 (RCCT) setting to both advance the science of cancer treatment-related oral complications and to improve patient care. Therefore, the purpose of this RCCT 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.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Allogeneic transplant patients who are enrolled in the participating NHLBI ABMT protocols, and are willing to participate in this study concurrently;
Have a diagnosis of oral cGVHD as confirmed by surgical biopsy results;
Able to understand and sign protocol consent;
Ages 18 to 80 years.
EXCLUSION CRITERIA:
Pregnant or lactating females for main study;
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, antidepressants);
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 anti0fungals, or mouthwashes);
Requiring addition of new systemic therapy including thalidomide, steroids, or radiation therapy;
Use of sedatives (including CNS depressants).

Maryland
      (NINR), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  040069; 04-NR-0069
Record last reviewed:  December 23, 2004
Last Updated:  December 30, 2004
Record first received:  December 30, 2003
ClinicalTrials.gov Identifier:  NCT00075023
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08