Clinical trial NCT01557517: Clobetasol for Oral Graft-Versus-Host Disease
Official title: A Randomized Double-Blind Pilot Study of Topical Clobetasol 0.05% Oral Rinse for Oral Chronic Graft-Versus-Host-Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Oral Chronic Graft vs Host Disease
Keywords: cGVHD
Oral cGVHD
Topical
Oral Rinse
Clobetasol
Oral Graft-Versus-Host Disease
GVHD
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2012-03-19
Enrollment: 40
Sex: ALL
Minimum age (years): 12
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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....

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 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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Percentage of Participants With a Response as Assessed by the 273-point Oral Mucositis Rating Scale (OMRS) Who Received Topical Clobetasol 0.05% Oral Rinse for Oral Chronic Graft-versus-host-disease (cGVHD) During a Four-week Treatment Period
timeFrame: At 4 weeks on active treatment
Secondary outcomes:
measure: Percent Change in Participants' Raw Score of Oral cGVHD Related Pain on a 0-10 Rating Scale
timeFrame: Baseline to Day 14 and baseline to Day 28
measure: Percent Change in Participants' Raw Score of Oral cGVHD Related Sensitivity on a 0-10 Rating Scale
timeFrame: Baseline and 4 weeks on active treatment
measure: Percent Change in Participants' Raw Score of Oral cGVHD Related Dryness on a 0-10 Rating Scale
timeFrame: Baseline and 4 weeks on active treatment
measure: Maximum Plasma Concentration (Cmax) of Clobetasol During Pharmacokinetic Testing
timeFrame: pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse
measure: Plasma Concentrations of Clobetasol Mouth Rinse in cGVHD Patients at Baseline (Day 0) and Day 28
timeFrame: Baseline Day 0 and Day 28
measure: Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
timeFrame: Date treatment consent signed to date off study, approximately 62 months and 12 days.
measure: Time to Maximum Plasma Concentration (Cmax) of Clobetasol
timeFrame: pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse
measure: Area Under the Plasma Concentration vs Time Curve for All Time Points
timeFrame: pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Najla El Jurdi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/j.tripleo.2005.08.028.
citation: 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. doi: 10.1038/sj.bmt.1705490. Epub 2006 Sep 18.
citation: 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. doi: 10.1182/blood-2002-01-0011.