Topical Dexamethasone and Tacrolimus for the Treatment of Oral Chronic Graft-Versus-Host Disease

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00686855
• Collaborator: Dana-Farber Cancer Institute (Other), Boston Children's Hospital (Other), Beth Israel Deaconess Medical Center (Other), Massachusetts General Hospital (Other)
• Enrollment: 46
• Locations: 5
• Arms: 2
• Duration (Months): 55
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine the effectiveness of topical steroid therapy (with a drug called dexamethasone) and topical tacrolimus therapy for the treatment of oral chronic Graft-Versus-Host Disease (cGVHD)

Condition or Disease	Intervention/Treatment	Phase
Oral Chronic Graft-versus-host Disease	Drug: Tacrolimus; Drug: Dexamethasone	Phase 2

Detailed Description

• Because no one knows which study option is best, participants will be "randomized" into one of two study groups: topical dexamethasone or topical tacrolimus.

• Participants will take the medication by mouth rinse four times a day for 5 minutes at a time. After rinsing they will spit out the medication and will not be able to eat or drink for 15 minutes.

• Participants will also take anti-fungal medication (fluconazole) orally once a week.

• After two weeks on study treatment, participants will have a blood drawn to monitor tacrolimus levels.

• After the final treatment (4 weeks), participants will have the following tests and procedures: clinical examination; questionnaire; blood tests; oral culture; optional tissue biopsy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Phase II Randomized Trial of Topical Dexamethasone and Tacrolimus for the Treatment of Oral Chronic Graft-Versus-Host Disease
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tacrolimus Tacrolimus Arm Closed to Accrual as of January 2012	Drug: Tacrolimus; Tacrolimus elixir taken as an oral rinse four times a day for 4 weeks
Experimental: Dexamethasone	Drug: Dexamethasone; Dexamethasone elixir taken as an oral rinse 4 times a day for 4 weeks

Outcome Measures

Primary Outcome Measures

1. The Clinical Efficacy of Topical Steroid and Topical Tacrolimus Therapies for the Treatment of Oral cGHVD. [Participants were assessed at Baseline and 4 weeks after start of therapy]

   Participants were given a survey at the time of screening and 4 weeks after start of therapy. The participants self-reported three symptoms of oral cGVHD: oral sensitivity, mouth pain, and mouth dryness. Each symptom was given a score ranging from 0-10, with 0 as none and 10 as the worst. Improvement in subjective scores was defined as 3 points or further reduction from pre-treatment to post-treatment assessment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with oral chronic graft-versus-host disease

• Patients 4 years of age or older

• Stable cGVHD medication regimen for the four weeks prior to study enrollment

Exclusion Criteria:

• Patients already on topical steroid or tacrolimus therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Children's Hospital Boston	Boston	Massachusetts	United States	02115
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Beth-Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Brigham and Women's Hospital
• Dana-Farber Cancer Institute
• Boston Children's Hospital
• Beth Israel Deaconess Medical Center
• Massachusetts General Hospital

Investigators

• Principal Investigator: Nathaniel Treister, DMD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nathaniel S. Treister, DMD, DMSc, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00686855
• Other Study ID Numbers: 08-027
• First Posted: May 30, 2008
• Last Update Posted: Mar 20, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Nathaniel S. Treister, DMD, DMSc, Principal Investigator, Dana-Farber Cancer Institute: tacrolimus; dexamethasone; oral rinse
• Additional relevant MeSH terms: Graft vs Host Disease; Dexamethasone; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Dexamethasone	Tacrolimus
Arm/Group Description	Dexamethasone : Dexamethasone elixir taken as an oral rinse 4 times a day for 4 weeks	Tacrolimus Arm Closed to Accrual as of January 2012 Tacrolimus : Tacrolimus elixir taken as an oral rinse four times a day for 4 weeks
Period Title: Overall Study
STARTED	28	18
COMPLETED	27	17
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Dexamethasone	Tacrolimus	Total
Arm/Group Description	Dexamethasone : Dexamethasone elixir taken as an oral rinse 4 times a day for 4 weeks	Tacrolimus Arm Closed to Accrual as of January 2012 Tacrolimus : Tacrolimus elixir taken as an oral rinse four times a day for 4 weeks	Total of all reporting groups
Overall Participants	28	18	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 78.6%	12 66.7%	34 73.9%
>=65 years	6 21.4%	6 33.3%	12 26.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (11.5)	54.9 (15.3)	54.2 (13)
Sex: Female, Male (Count of Participants)
Female	17 60.7%	6 33.3%	23 50%
Male	11 39.3%	12 66.7%	23 50%
Region of Enrollment (participants) [Number]
United States	28 100%	18 100%	46 100%

Outcome Measures

1. Primary Outcome

Title	The Clinical Efficacy of Topical Steroid and Topical Tacrolimus Therapies for the Treatment of Oral cGHVD.
Description	Participants were given a survey at the time of screening and 4 weeks after start of therapy. The participants self-reported three symptoms of oral cGVHD: oral sensitivity, mouth pain, and mouth dryness. Each symptom was given a score ranging from 0-10, with 0 as none and 10 as the worst. Improvement in subjective scores was defined as 3 points or further reduction from pre-treatment to post-treatment assessment.
Time Frame	Participants were assessed at Baseline and 4 weeks after start of therapy

Outcome Measure Data

Analysis Population Description

Of the 46 participants enrolled on the trial, 36 were deemed evaluable for response.

Arm/Group Title	Dexamethasone	Tacrolimus
Arm/Group Description	Dexamethasone : Dexamethasone elixir taken as an oral rinse 4 times a day for 4 weeks	Tacrolimus Arm Closed to Accrual as of January 2012 Tacrolimus : Tacrolimus elixir taken as an oral rinse four times a day for 4 weeks
Measure Participants	22	14
Improvement in Oral Sensitivity	15 53.6%	3 16.7%
Improvement in Mouth Pain	11 39.3%	2 11.1%
Improvement in Mouth Dryness	11 39.3%	5 27.8%
Improvement in 1 or more areas	17 60.7%	7 38.9%
Improvement in 2 or more areas	13 46.4%	2 11.1%
Improvement in all 3 areas	7 25%	1 5.6%

Adverse Events

Time Frame	Adverse events were collected during the four week peroid participants took the study treatment.
Arm/Group Title	Dexamethasone		Tacrolimus
Arm/Group Description	Dexamethasone : Dexamethasone elixir taken as an oral rinse 4 times a day for 4 weeks		Tacrolimus Arm Closed to Accrual as of January 2012 Tacrolimus : Tacrolimus elixir taken as an oral rinse four times a day for 4 weeks
All Cause Mortality
	Dexamethasone		Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexamethasone		Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		1/18 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/28 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Dexamethasone		Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/28 (3.6%)		1/18 (5.6%)
General disorders
Pain - Oral Cavity	1/28 (3.6%)	1	0/18 (0%)	0
Infections and infestations
Infection Gr0-2 neutrophils - oral cavity	0/28 (0%)	0	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.