Dexamethasone to Prevent Oral Chronic Graft-versus-Host Disease

NCT00391170 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 07000507-H-0005
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine if a dexamethasone mouth rinse can reduce the risk of developing oral chronic graft-versus-host disease (cGVHD) in patients who have undergone a bone marrow (stem cell) transplant procedure. cGVHD is a common complication of stem cell transplantation, resulting from the donor cells attacking the transplant recipient's tissues. In oral cGVHD, the tissues in the mouth are damaged, causing painful mouth sores. Dexamethasone is a corticosteroid that is commonly used to treat inflammation. It is the only corticosteroid available that can be used as a mouth rinse. Patients 12 years of age or older who have received a stem cell transplant may be eligible to participate if they are enrolled within 70 to 90 days of their transplant. Candidates are screened with a medical history and oral exam. Participants are randomly assigned to receive either the dexamethasone rinse or a placebo (a solution that looks and tastes like the dexamethasone rinse but has no active medication). They undergo the following procedures: Treatment with the study solution. Patients rinse their mouth with the dexamethasone solution or placebo three times a day for 3 months. Clinic visits before starting treatment and at 1, 2 and 3 months after starting the study drug for the following procedures:

• Oral exam (before starting treatment and at each visit).
• Photographs of the mouth (before starting treatment and at 3 months).
• Biopsy from inside the cheek (before starting treatment). The inside of the cheek is numbed and a small piece of tissue is removed for examination by a pathologist.
• Saliva sample collection (before starting treatment).
• Blood draw (before starting treatment and at each visit).
• Quality-of-life questionnaires (before starting treatment and at 3 months).
• Questionnaire to assess level of dry mouth and mouth pain (before starting treatment and at each visit).
• Review of medications (at each visit).
• ACTH stimulation test to evaluate adrenal gland function (at 3 months). Patients are given an injection of a drug called "ACTH" or "cosyntropin" which is a version of a hormone normally produced by the pituitary gland. Blood samples are drawn before the injection and at 30 and 60 minutes after the injection to measure levels of the hormone cortisol. After treatment ends, participants are contacted by telephone every month for 6 months to report any symptoms of cGVHD, and they return to the clinic at 6 months for a final evaluation.

Conditions

Graft vs Host Disease

Keywords

Oral Chronic GVHD; Topical Dexamethasone; Tissue Markers; Salivary Proteomics; Quality of Life; Oral Chronic Graft Versus Host Disease; Oral Pain; Mouth Pain

Outcome Measures

Primary Outcomes (1)

• Participants That Developed Severity Score 3 or Higher Oral Chronic Graft Versus Host Disease (GVHD).

  Participants that developed clinically significant (severity score 3 or higher) oral chronic graft versus host disease (GVHD) within 90 days of initiating treatment. Oral chronic GVHD is defined by Lichen Planus (Oral GVHD) Severity Scale (Thongprasom et al., 2003). Score 5: White striae with erosive area \> 1 cm\^2 Score 4: White striae with erosive area \< 1 cm\^2 Score 3: White striae with erythematous area \> 1 cm\^2 Score 2: White striae with erythematous area \< 1 cm\^2 Score 1: Mild white striae only Score 0: No lesions, normal mucosa

  Day 90

Secondary Outcomes (3)

• Participants With Chronic Oral Graft Versus Host Disease (GVHD) Based on Severity Scores

  Day 90

• Participants With Systemic Absorption of Topical Dexamethasone

  3 months

• Participants With Suppressed Adrenal Cortical Function Due to Topical Dexamethasone

  3 months

Study Arms (2)

Dexamethasone oral rinse in stem cell transplant participants

EXPERIMENTAL

Dexamethasone 0.01% (0.5mg/5 mL) oral rinse solution in post allogeneic hematopoietic stem cell transplant participants. Rinse oral cavity three times daily for two minutes with ten milliliters then expectorate. Complete for three months duration.

Drug: Topical Dexamethasone

Placebo oral rinse in stem cell transplant participants

PLACEBO COMPARATOR

Placebo oral rinse in post allogeneic hematopoietic stem cell transplant participants. Rinse oral cavity three times daily for two minutes with ten milliliters then expectorate. Complete for three months duration.

Drug: Placebo

Interventions

Topical Dexamethasone DRUG

dexamethasone 0.01%

Dexamethasone oral rinse in stem cell transplant participants

Placebo DRUG

Placebo

Placebo oral rinse in stem cell transplant participants

Eligibility Criteria

• Age: 12 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• History of allogeneic hematopoietic stem cell transplantation within 60-90 days of enrollment.
• Age 12 or older.
• Ability to rinse and expectorate study medication rather than swallow it.
• Ability and willingness to come to Clinical Center for follow-up appointments and at the time of development of symptoms/signs suggestive of oral GVHD.

You may not qualify if:

• Clinically significant oral chronic GVHD at the time of the screening.
• Active viral or fungal infection involving oral cavity not resolving by day 90.
• Platelet count less than 20,000/ml at the time of the screening appointment.
• Life expectancy less than 4 months at the time of enrollment.
• Documented hypersensitivity to dexamethasone.
• Pregnancy or lactation.
• Inability to understand the investigational nature of the study.
• Inability to provide informed consent.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Chakrabarti S, Childs R. Allogeneic immune replacement as cancer immunotherapy. Expert Opin Biol Ther. 2003 Oct;3(7):1051-60. doi: 10.1517/14712598.3.7.1051.

  PMID: 14519070 BACKGROUND

• Tykodi SS, Warren EH, Thompson JA, Riddell SR, Childs RW, Otterud BE, Leppert MF, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation for metastatic renal cell carcinoma after nonmyeloablative conditioning: toxicity, clinical response, and immunological response to minor histocompatibility antigens. Clin Cancer Res. 2004 Dec 1;10(23):7799-811. doi: 10.1158/1078-0432.CCR-04-0072.

  PMID: 15585611 BACKGROUND

• Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003 Apr;9(4):215-33. doi: 10.1053/bbmt.2003.50026.

  PMID: 12720215 BACKGROUND

• Thongprasom K, Luengvisut P, Wongwatanakij A, Boonjatturus C. Clinical evaluation in treatment of oral lichen planus with topical fluocinolone acetonide: a 2-year follow-up. J Oral Pathol Med. 2003 Jul;32(6):315-22. doi: 10.1034/j.1600-0714.2003.00130.x.

  PMID: 12787037 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Clara, Joseph
• Organization: National Heart Lung and Blood Institute

joseph.clara@nih.gov

+1 301 402 2399

Study Officials

• Joseph A Clara, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2006
• First Posted: October 23, 2006
• Study Start: November 24, 2006
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: February 10, 2022
• Results First Posted: February 10, 2022

Record last verified: 2021-02-24

Locations

US (1)