Clobetasol for Oral Graft-Versus-Host Disease

NCT01557517 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 12006812-C-0068
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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....

Conditions

Oral Chronic Graft vs Host Disease

Keywords

cGVHD; Oral cGVHD; Topical; Oral Rinse; Clobetasol; Oral Graft-Versus-Host Disease; GVHD

Outcome Measures

Primary Outcomes (1)

• 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

  Mucosal changes were assessed by the Oral Mucositis Rating Scale. The primary endpoint was evaluated using the OMRS. Oral tissue changes are rated on a scale of 0-3 compared with normal oral tissue (0-normal/no change, 1-mild change, 2-moderate change, and 3-severe change). Total score is the sum of all OMRS items with a possible range of 0. Total score is the sum of all OMRS items with a possible range of 0-273. Lower score=more normal oral mucosa. There is no standard definition of response in this field. Definitions we used in this pilot study to grade the response to study intervention are: Progress of 25% of initial score (rounded to the closest number) on the OMRS scale. Completion (PD) is defined as an increase of 25% of initial score (rounded to the closest number). Partial Response (PR) is defined as a decrease Response (CR) is defined as a PR plus a score of 0 on the erythema and ulceration components. Stable Disease (SD) does not meet criteria for progression or response.

  At 4 weeks on active treatment

Secondary Outcomes (8)

• Percent Change in Participants' Raw Score of Oral cGVHD Related Pain on a 0-10 Rating Scale

  Baseline to Day 14 and baseline to Day 28

• Percent Change in Participants' Raw Score of Oral cGVHD Related Sensitivity on a 0-10 Rating Scale

  Baseline and 4 weeks on active treatment

• Percent Change in Participants' Raw Score of Oral cGVHD Related Dryness on a 0-10 Rating Scale

  Baseline and 4 weeks on active treatment

• Maximum Plasma Concentration (Cmax) of Clobetasol During Pharmacokinetic Testing

  pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse

• Plasma Concentrations of Clobetasol Mouth Rinse in cGVHD Patients at Baseline (Day 0) and Day 28

  Baseline Day 0 and Day 28

Study Arms (2)

Clobetasol

EXPERIMENTAL

Patients will rinse oral cavity with 10cc of clobetasol 0.05% for 2 minutes 3 times a day.

Drug: Clobetasol Oral Rinse

Placebo

PLACEBO COMPARATOR

Patients will rinse oral cavity with 10cc of placebo oral rinse for 2 minutes 3 times a day.

Drug: Placebo oral rinse

Interventions

Clobetasol Oral Rinse DRUG

Cycle= up to 4 weeks Patients will rinse oral cavity with 10cc of clobetasol 0.05% oral rinse for 2 minutes 3 times a day.

Clobetasol

Placebo oral rinse DRUG

Patients will rinse oral cavity with 10cc of placebo oral rinse for 2 minutes 3 times a day.

Placebo

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 16448918 BACKGROUND

• 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.

  PMID: 16980994 BACKGROUND

• 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.

  PMID: 12091330 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: Dr. Najla El Jurdi
• Organization: National Cancer Institute

najla.eljurdi@nih.gov

240-992-4033

Study Officials

• Najla El Jurdi, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 16, 2012
• First Posted: March 19, 2012
• Study Start: March 28, 2012
• Primary Completion: June 9, 2017
• Study Completion: August 24, 2017
• Last Updated: June 15, 2025
• Results First Posted: January 3, 2019

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)