Clobetasol for Oral Graft-Versus-Host Disease

A Randomized Double-Blind Pilot Study of Topical Clobetasol 0.05% Oral Rinse for Oral Chronic Graft-Versus-Host-Disease

Background:

- Oral graft-versus-host disease (GVHD) is a possible complication of bone marrow transplants. It is the result of the donor cells trying to attack the recipients body. Symptoms include dry mouth, sensitivity and pain when tasting certain spices and flavors, and painful swallowing. Steroids are a possible effective treatment for GHVD, but they can cause side effects when given as pills or injections. Steroids given in a cream or rinse form, applied directly to the site of the symptoms, can have fewer side effects. However, their effectiveness as a rinse has not been tested in the mouth. Researchers want to see if a steroid called clobetasol can be used as a mouth rinse to treat oral GHVD.

Objectives:

- To see if a clobetasol rinse is a safe and effective treatment for oral graft-versus-host disease.

Eligibility:

- Individuals at least 12 years of age who have oral GHVD and are not allergic to clobetasol.

Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. They will also have an oral exam, a mouth tissue biopsy, and other tests before starting the study drug.
• Participants will be separated into two groups. One group will receive clobetasol; the other will have a placebo liquid.
• Participants will rinse their mouths with the study liquid three times a day after meals for 2 weeks.
• After 2 weeks, participants will have another study visit with blood tests and other exams.
• After the study visit, all participants will start to use the clobetasol rinse. Those who originally had clobetasol will use the rinse for another 2 weeks. Those who originally had a placebo will use the rinse for 4 weeks.
• Participants will have a follow-up exam after the end of treatment....

BACKGROUND:

• Chronic Graft versus Host Disease (cGVHD) is a major late complication of allogeneic hematopoietic stem cell transplantation.
• The oral cavity is the second most commonly affected area in cGVHD and is a major cause of morbidity.
• Clobetasol is a high-potency topical corticosteroid widely used for a variety of inflammatory disorders of the skin and oral mucosa.
• Treatment of oral cGVHD by topical agents is an attractive strategy to potentially avoid adverse effects associated with systemic immunosuppression.

OBJECTIVES:

- To investigate efficacy of topical clobetasol 0.05% oral rinse for oral chronic graft versus-host disease (cGVHD)

ELIGIBILITY:

- Patients age 12-99 years with clinically significant oral cGVHD.

DESIGN:

• This is a randomized, double blind, placebo-controlled, pilot study of clobetasol 0.05% topical oral rinse with an open label extension period.
• Patients will rinse oral cavity with 10cc of clobetasol 0.05% or placebo oral rinse for 2 minutes 3 times a day.
• Treatment duration will be for 2 weeks in the randomized phase and 2-4 weeks in the open label phase.
• Up to 40 patients will be enrolled on this pilot trial until 34 evaluable patients are assessed.

• INCLUSION CRITERIA:
• Age: 12 years 99 years.
• Diagnosis: clinically significant oral chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) with severity score of at least 2 on erythema subset and/or at least 1 on ulceration subset and a composite score greater than or equal to 20 of the Oral Mucositis Rating Scale (OMRS) scale confirmed by the principal investigator (PI), clinical study chair (CSC), or lead associate investigator (LAI).
• Hematologic Function: Patients must have a platelet count greater than or equal to 20,000/microL at the time of the initial evaluation.
• Informed Consent: All patients or their legal representative (for patients <18 years old) must sign an institutional review board (IRB) approved informed consent document (cGVHD natural history protocol 04-C-0281 or any National Cancer Institute (NCI) protocol allowing for screening procedures) prior to performing studies to determine patient eligibility. After confirmation of patient eligibility all patients or their legal representative must sign the protocol specific informed consent. For pediatric patients age appropriate assent will be obtained in accordance with National Institutes of Health (NIH) guidelines.
• Patients must be able to rinse and expectorate study medication rather than swallow it. Female patients must be willing to practice birth control (including abstinence) during and for two months after treatment, if of childbearing potential.
• Patients must have the ability and willingness to come to Clinical Center for bi-weekly follow-up appointments.
• No change in systemic immunosuppressive therapy (type or intensity level) within 2 weeks prior to enrollment.
• A 7-day washout period is required if patients are currently using another oral topical treatment for mouth lesions. Patients currently using clobetasol oral topical treatment are not eligible for this study.

EXCLUSION CRITERIA:

• Documented hypersensitivity to clobetasol.
• Use of clobetasol ointment intra-orally at any time during the last 6-month period.
• Pregnant or breast-feeding females due to possible toxicity to the fetus or infant.
• Inability to understand the investigational nature of the study to provide informed consent.
• Patients who, for medical or other reasons, are unable to comply with the study procedures.