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Evaluation of Efficacy and Mechanisms of Topical Thalidomide for Chronic Graft-Versus-Host-Disease Related Stomatitis

Phase 2
18 Years
80 Years
Not Enrolling
Graft vs Host Disease, Stomatitis, Bone Marrow Transplantation

Thank you

Trial Information

Evaluation of Efficacy and Mechanisms of Topical Thalidomide for Chronic Graft-Versus-Host-Disease Related Stomatitis

Oncology patients undergoing allogeneic bone marrow/peripheral blood stem cell transplant
(HSCT) frequently experience an allo-immune condition termed graft-versus-host-disease
(GVHD). The pathogenesis of GVHD derives from an immune attack mediated by donor T-cells
recognizing antigens expressed on normal tissues of the patient. This condition occurs in
HSCT rather than autologous BMT because of disparities in minor histocompatibility antigens
between donor and recipient, inherited independently of HLA genes (Lazarus, Vogelsang, and
Rowe, 1997). GVHD may be conceptualized as a cytokine storm stemming from an outpouring
of endogenous cytokines resulting in many tissue effects (Lazrarus et al, 1997). Oral
chronic GVHD (cGVHD), which is classically diagnosed as a late complication of HSCT
occurring more than 100 days post transplant, presents with tissue atrophy and erythema,
lichenoid changes (hyperkeratotic striae, patches, plaques, and papules) and
pseudomembranous ulcerations typically occurring on the buccal and labial mucosa and the
lateral tongue, mucoceles due to inflammation of minor salivary glands, and xerostomia
(Lloid, 1995). The ulcerative phase often leads to a cascade of negative sequelae including
oropharyngeal pain, critical treatment alterations or cessation, diminished capacity for
food intake, and decreased quality of life. We hypothesize that the mechanisms of tissue
injury occurring at the mucosal level leading to cGVHD-related stomatitis are similar to
other types of stomatitis, such as chemotherapy-related and aphthous stomatitis, and are
therefore amenable to treatment with anti-inflammatory strategies.

Optimal treatment strategies for cGVHD-related ulcerative stomatitis and related
oropharyngeal pain have not been established. Therefore, there is a critical need to examine
the pathogenesis of and to evaluate interventions for cGVHD-related ulcerative stomatitis
and related acute oropharyngeal pain in the randomized controlled clinical trial setting to
both advance the science of cancer treatment-related oral complications and to improve
patient care. Therefore, the purpose of this study is to elucidate the role of inflammation
in GVHD-related ulcerative stomatitis by testing the efficacy of topical thalidomide on the
resolution of cGVHD-related stomatitis and related oropharyngeal pain. The actions of
thalidomide, which include inhibition of the release of tumor necrosis factor-alpha (TNFa)
and resultant alteration of the inflammatory cascade, may provide insight into the role of
local mucosal inflammation in cGVHD-related stomatitis.

Inclusion Criteria


Participating in HSCT or cGVHD protocols and willing to participate in this study

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.


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

Use of sedatives (including CNS depressants);

Absolute neutrophil count (ANC) less than 750/mm(3)

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Progress in oral ulcer healing.

Safety Issue:



United States: Federal Government

Study ID:




Start Date:

December 2003

Completion Date:

April 2010

Related Keywords:

  • Graft Vs Host Disease
  • Stomatitis
  • Bone Marrow Transplantation
  • Stomatitis
  • Oropharyngeal Pain
  • TNF-Alpha
  • Allogeneic BMT
  • Inflammation
  • Graft vs Host Disease
  • Stomatitis



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892
Fred Hutchinson Cancer Research Center Seattle, Washington  98109