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Clobetasol for Oral Graft-Versus-Host Disease

Primary Purpose

Oral Chronic Graft vs Host Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Clobetasol Oral Rinse

Placebo oral rinse

About this trial

This is an interventional treatment trial for Oral Chronic Graft vs Host Disease focused on measuring cGVHD, Oral cGVHD, Topical, Oral Rinse, Clobetasol, Oral Graft-Versus-Host Disease, GVHD

Eligibility Criteria

12 Years - 99 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Clobetasol

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Oral cavity pain was assessed by an oral cavity specific quality of life questionnaire. Pain was rated based on a 0-10 rating scale on which subjects selected a single integer. 0 = no pain and 10 = worst pain. A negative value indicates an increase in oral pain. A positive value indicates an improvement in patient-perceived oral pain.

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

Oral cavity sensitivity was assessed by an oral cavity specific quality of life questionnaire. Sensitivity was rated based on a 0-10 rating scale on which subjects selected a single integer. 0 = no sensitivity and 10 = worst sensitivity. A negative value indicates an increase in oral sensitivity. A positive value indicates an improvement in patient-perceived oral sensitivity.

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

Oral cavity dryness was assessed by an oral cavity specific quality of life questionnaire. Dryness was rated based on a 0-10 rating scale on which subjects selected a single integer. 0 = no dryness and 10 = worst dryness. A negative value indicates an increase in patient-perceived oral dryness. A positive value indicates an improvement in patient-perceived oral dryness.

Maximum Plasma Concentration (Cmax) of Clobetasol During Pharmacokinetic Testing

Steady-state pharmacokinetics of systemic clobetasol were assessed following a single 2 min oral rinse of 0.05% clobetasol on day 14 (1 patient collected on day 12). A noncompartmental pharmacokinetic assessment was performed using WinNonlin v5 (Pharsight Corp, Mountain View, CA) from three sampling times (pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse). Plasma concentrations of clobetasol were measured using a newly designed and validated LC-MS/MS assay, with a lower limit of quantification of 0.05 ng/mL. The maximum plasma concentrations (CMAX) were recorded as observed values and the area under the plasma-concentration time curve using all three sampling time points (AUCALL) was calculated using the Linear Trapezoidal rule.

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

Peripheral blood was drawn at baseline and day 28 of clobetasol rinse use, and clobetasol levels were measured in the blood sample. Plasma concentrations of clobetasol were measured using a validated LC-MS/MS assay with a lower limit of quantification of 0.05 ng/mL. Any values below detectable limit or with no peak were adjusted to 0.

Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time to Maximum Plasma Concentration (Cmax) of Clobetasol

Area Under the Plasma Concentration vs Time Curve for All Time Points

Full Information

NCT ID

NCT01557517

First Posted

March 16, 2012

Last Updated

December 10, 2018

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01557517

Brief Title

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

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

January 26, 2012 (Actual)

Primary Completion Date

June 9, 2017 (Actual)

Study Completion Date

August 24, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Oral Chronic Graft vs Host Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Clobetasol

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Clobetasol Oral Rinse

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo oral rinse

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

Time Frame

At 4 weeks on active treatment

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline to Day 14 and baseline to Day 28

Title

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

Description

Time Frame

Baseline and 4 weeks on active treatment

Title

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

Description

Time Frame

Baseline and 4 weeks on active treatment

Title

Maximum Plasma Concentration (Cmax) of Clobetasol During Pharmacokinetic Testing

Description

Time Frame

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

Title

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

Description

Time Frame

Baseline Day 0 and Day 28

Title

Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

Description

Time Frame

Date treatment consent signed to date off study, approximately 62 months and 12 days.

Title

Time to Maximum Plasma Concentration (Cmax) of Clobetasol

Description

Time Frame

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

Title

Area Under the Plasma Concentration vs Time Curve for All Time Points

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven Z Pavletic, M.D.

Organizational Affiliation

National Cancer Institute (NCI)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center, 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

16448918

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.

Results Reference

background

PubMed Identifier

16980994

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.

Results Reference

background

PubMed Identifier

12091330

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.

Results Reference

background

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-C-0068.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

Clobetasol for Oral Graft-Versus-Host Disease

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