Clobetasol for Oral Graft-Versus-Host Disease

Condition(s) targeted: Oral Chronic Graft vs Host Disease

Intervention: Clobetasol Oral Rinse (Drug); Placebo oral rinse (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Steven Z Pavletic, M.D., Principal Investigator, Affiliation: National Cancer Institute (NCI)

Overall contact:
Licia Masuch, Phone: (301) 435-9352, Email: licia.masuch@nih.gov

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 recipient s 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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: To investigate efficacy of topical clobetasol 0.05% oral rinse for oral chronic graft-versus-host-disease (cGVHD) during a four-week treatment period as assessed by Oral Mucositis Rating Scale (OMRS).

Secondary outcome:

To assess the effect of topical clobetasol on oral cGVHD related pain, sensitivity, and dryness.

To evaluate the basic pharmacodynamics and pharmacokinetics of clobetasol mouth rinse in cGVHD patients.

Detailed description: 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

graftversus-host disease (cGVHD)

- To assess the effect of topical clobetasol on oral cGVHD related pain, sensitivity, and

dryness.

- To evaluate the basic pharmacodynamics and pharmacokinetics of clobetasol mouth rinse

in cGVHD patients.

- To obtain a pilot assessment of patient perceived oral health in cGHVD and its response

to treatment with topical clobetasol.

- To evaluate the psychometrics of the NIH Oral cGVHD Clinical Scoring instrument.

- To evaluate the immunological profile present at baseline and after clobetasol

treatment in oral tissue to identify potential biomarkers for disease response or resistance to clobetasol.

- To evaluate blood and saliva to identify potential biomarkers for oral cGVHD disease

activity and response to topical clobetasol. 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.

- A maximum of 34 evaluable patients will be enrolled on this pilot trial.

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

- Age: 12 years 99 years.

- Diagnosis: clinically significant oral cGVHD after allogeneic 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 IRB approved informed consent document (cGVHD natural history protocol 04-C-0281 or any 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 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.

Licia Masuch, Phone: (301) 435-9352, Email: licia.masuch@nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, Phone: (888) NCI-1937

NIH Clinical Center Detailed Web Page

Related publications:

Imanguli MM, Pavletic SZ, Guadagnini JP, Brahim JS, Atkinson JC. Chronic graft versus host disease of oral mucosa: review of available therapies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Feb;101(2):175-83. Review.

Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant. 2006 Nov;38(10):645-51. Epub 2006 Sep 18. Review.

Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Bensinger WI, Storb R, Appelbaum FR, Forman SJ, Blume KG, Martin PJ. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood. 2002 Jul 15;100(2):415-9.

Starting date: January 2012
Last updated: October 21, 2014