An Open Label Phase II Trial of Topical Sirolimus for the Treatment of Refractory Oral Chronic Graft-versus-Host-Disease
Condition: Chronic Graft-versus-Host-Disease; Oral Mucosal Disease Due to Graft-versus-host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Sirolimus
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: Chronic Graft-versus-Host-Disease; Oral mucosal disease

Summary:

      This research study is evaluating the effectiveness of topical sirolimus combined with
      topical steroid therapy, as a possible treatment for oral cGVHD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  While there will be no restrictions on concurrent systemic medications, all subjects
             must be on a stable immunomodulatory medication regimen for 7 days prior to beginning
             the study without plans to adjust doses during the following four-week study period.
             Dose modifications to maintain therapeutic drug levels of immunosuppressants (i.e.
             tacrolimus and sirolimus) during the study intervention period are allowed and do not
             constitute a trial violation. Changes in medications for non-cGVHD medical conditions
             will not affect eligibility.

          -  Age 4 years and older.

          -  Patients with symptomatic oral chronic graft-versus-host disease (sensitivity score ≥
             4).

          -  Stable topical steroid therapy with dexamethasone, clobetasol, or budesonide oral
             solutions (5 min, four times a day) for seven days prior to study enrollment.

          -  Stable systemic cGVHD medication regimen for seven days prior to study enrollment.
             Dose modifications to maintain therapeutic drug levels of immunosuppressants (i.e.
             tacrolimus and sirolimus) for the month prior and during the study intervention period
             are allowed and do not constitute a trial violation.

          -  The effects of sirolimus on the developing human fetus are unknown. For this reason
             and because immunosuppressants agents as well as other therapeutic agents used in this
             trial are known to be teratogenic, women of child-bearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry and for the duration of study participation. Should a
             woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately. Men
             treated or enrolled on this protocol must also agree to use adequate contraception
             prior to the study, for the duration of study participation, and 4 months after
             completion of topical sirolimus administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients already using topical sirolimus therapy.

          -  Patients who have an allergy/intolerance to sirolimus.

          -  Sensitivity score ≤ 3.

          -  Inability to comply with study instructions.

          -  Pregnant or breastfeeding.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded due to the potential for teratogenic or abortifacient
             effects. Because there is an unknown but potential risk for adverse events in nursing
             infants, breastfeeding should be discontinued if the mother is treated with sirolimus.

          -  HIV-positive participants on combination antiretroviral therapy are ineligible because
             of the potential for pharmacokinetic interactions with sirolimus. In addition, these
             participants are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in participants
             receiving combination antiretroviral therapy when indicated.