Effectiveness of Topical Thalidomide to Treat Chronic Graft-Versus-Host-Disease Related Stomatitis

NCT00075023 | Terminated Phase 2 Results DMC

• 2 other identifiers: 04006904-NR-0069
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This study was designed to be conducted in 2 parts. The first part is a pilot study to test the effects of topical thalidomide gel 20mg applied to up to 3 oral ulcers in patients who have developed oral chronic graft-versus-host-disease (cGVHD)-related ulcerative stomatitis following allogeneic bone marrow/peripheral blood stem cell transplant (HSCT). Chronic GVHD may be related to increased levels of a cytokine called TNF-alpha (TNFa) following HSCT. Thalidomide's anti-inflammatory effects may lower TNFa levels, lead to healing of these oral ulcers, and decrease oral pain. If the pilot study is successful, the second part of the study will be done. This will test the effects of a 0.1% (20mg) thalidomide mouthwash in treating oral cGVHD-related stomatitis in patients following allogeneic HSCT. Applying thalidomide directly to the GVHD-related mouth ulcer in gel form or to the entire oral cavity in mouthwash form rather than taking it in pill form may reduce the amount of drug that enters the blood stream and cause less side effects. In the pilot study, participants will be randomly assigned to receive thalidomide gel 20mg or placebo (identical gel with no thalidomide) to use 4 times a day for 4 weeks. In the mouthwash study, participants will be randomly assigned to receive 0.1% 20mg thalidomide mouthwash or placebo (identical mouth rinse with no thalidomide) to use 4 times a day for 4 weeks. Participants will undergo the following procedures before beginning experimental treatment, then once a week for 4 weeks, and then approximately 8 weeks after the first visit:

• Interview about current medications and use of alcohol and cigarettes
• Self-report of mouth and throat pain
• Oral examination for stomatitis rating, and oral ulcer(s) measurement
• Quality of life questionnaire (repeated only at week 8 of the study)
• Mouth photography to measure and record the oral ulcer response to treatment
• Saliva sampling to look for proinflammatory cytokines (small proteins), including TNFa
• Oral ulcer exudate collected by filter paper to obtain fluid for measuring TNFa levels
• Gentle swabbing of oral ulcers to culture for virus, fungus, and bacteria that may be present
• Small punch biopsy of the area near the ulcer or affected area to check for presence of TNFa (repeated only at week 4 of the study)
• Blood sampling to monitor TNFa levels
• A urine pregnancy test for women who are able to have children (repeated at weeks 2, 4, and 8)

Conditions

Graft-versus-Host Disease; Stomatitis

Keywords

Stomatitis; Oropharyngeal pain; TNF-alpha; Allogeneic hematopoietic stem cell transplant; Inflammation; Thalidomide; Oral chronic graft-versus-host disease

Outcome Measures

Primary Outcomes (1)

• Mean Percentage Change in Total Surface Area of Oral Ulceration.

  Mean percentage change in total surface area of oral ulceration

  baseline to 4 weeks

Study Arms (2)

Thalidomide gel

EXPERIMENTAL

Thalidomide gel 20 mg applied topically 4 times daily for 4 weeks to a maximum of 3 target oral ulcers

Drug: Thalidomide Gel

Placebo

EXPERIMENTAL

Placebo gel with no Thalidomide applied topically 4 times daily for 4 weeks to a maximum of 3 target oral ulcers

Drug: Placebo Gel

Interventions

Thalidomide Gel DRUG

Thalidomide gel

Placebo Gel DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participating in HSCT or cGVHD protocols and willing to participate in this study concurrently;
• Diagnosed with oral cGVHD stomatitis confirmed by surgical biopsy results;
• Oral ulceration present
• Able to understand and sign protocol informed consent;
• Ages 18 to 80 years of age.

You may not qualify if:

• Pregnant or lactating females;
• For the proof of concept study, females who are not surgically sterilized by means of hysterectomy or tubal ligation;
• For the main study, females of childbearing potential who do not agree to the use of two forms of highly effective contraception for at least four weeks prior, during, and for four weeks following the last dose of study drug;
• Sexually active males who do not agree to the use of a latex condom while receiving study drug and for four weeks following the last dose of study drug;
• Unwilling to follow precautions for use of thalidomide;
• Unable to demonstrate appropriate use of study medication;
• Concurrent use of non-protocol-related medications confounding assessment of the inflammatory response (antihistamines, non-steroidal anti-inflammatory drugs);
• Allergic reaction to thalidomide;
• Pre-existing oral infection, which might maximize the possibility of an infection or sepsis contributing to a drug-related adverse event;
• Unwilling or unable to forego concurrent treatment for mucosal lesions and/or related oral pain (including topical steroids, viscous lidocaine, topical anti-fungals);
• Requiring addition of new systemic therapy including thalidomide, steroids, or radiation therapy;
• Use of sedatives (including CNS depressants);
• Absolute neutrophil count (ANC) less than 750/mm(3)

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead
• Fred Hutchinson Cancer Center: collaborator

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 28104, United States

Location

Related Publications (4)

• Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol. 1999 Jan;70(1):13-29. doi: 10.1902/jop.1999.70.1.13.

  PMID: 10052767 BACKGROUND

• Antin JH, Ferrara JL. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992 Dec 15;80(12):2964-8.

  PMID: 1467511 BACKGROUND

• Aucott DM, Ashley FP. Assessment of the WHO partial recording approach in identification of individuals highly susceptible to periodontitis. Community Dent Oral Epidemiol. 1986 Jun;14(3):152-5. doi: 10.1111/j.1600-0528.1986.tb01521.x.

  PMID: 3459612 BACKGROUND

• St John L, Gordon SM, Childs R, Marquesen M, Pavletic SZ, Wu TX, Cozzarelli T, Schroeder E, Saria MG, Fall-Dickson JM. Topical thalidomide gel in oral chronic GVHD and role of in situ cytokine expression in monitoring biological activity. Bone Marrow Transplant. 2013 Apr;48(4):610-1. doi: 10.1038/bmt.2012.178. Epub 2012 Sep 24. No abstract available.

  PMID: 23000649 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease; Stomatitis; Inflammation

Condition Hierarchy (Ancestors)

Immune System Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Small sample size due to difficult enrollment

Results Point of Contact

• Title: Suzanne Wingate
• Organization: NINR/NIH

suzanne.wingate@nih.gov

301-827-0982

Study Officials

• Jane Fall-Dickson, RN, PhD

  NIH/NINR

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: December 30, 2003
• First Posted: December 31, 2003
• Study Start: December 1, 2003
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: November 4, 2015
• Results First Posted: November 4, 2015

Record last verified: 2015-10

Locations

US (2)