An Open Label Phase II Trial of Topical Sirolimus for the Treatment of Refractory Oral Chronic Graft-versus-Host-Disease

NCT ID: NCT02123966

Last Updated: 2018-07-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-05-31

Brief Summary

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

Detailed Description

Topical steroid therapy can be effective in managing oral cGVHD symptoms. However, a certain proportion of participants will not experience an adequate response to topical steroids and continue to have some degree of discomfort. Sirolimus is a non-steroidal immunosuppressive medication that has demonstrated efficacy in the management of cGVHD. Based on this, it is believed that a topical formulation applied inside the mouth may also demonstrate efficacy on a localized basis.

The purpose of this study is to assess the safety and efficacy of topical sirolimus as a swish and spit solution for the treatment of oral cGVHD in participants that have not had an adequate clinical response to topical steroid therapy alone.

Conditions

Chronic Graft-versus-Host-Disease; Oral Mucosal Disease Due to Graft-versus-host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Topical Sirolimus + Steroid

A four week supply of topical sirolimus will be dispensed. The treatment instructions will be to rinse and spit (NOT swallow) with one teaspoon (5 mL) of sirolimus solution 0.1mg/mL, combined with one teaspoon (5 mL) of steroid solution (dexamethasone 0.1%, clobetasol 0.05%, or budesonide 0.03%, based on the ongoing topical steroid prescription at the time of study enrollment) four times a day for 5 minutes at a time, and not to eat or drink for 15 minutes afterwards.

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

Interventions

Sirolimus

Intervention Type: DRUG

Other Intervention Names

Rapamune®

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.

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Nathaniel S. Treister, DMD, DMSc

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nathaniel S Treister, DMD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

Reference Type: BACKGROUND

PMID: 25529383 (View on PubMed)

Slade GD. Derivation and validation of a short-form oral health impact profile. Community Dent Oral Epidemiol. 1997 Aug;25(4):284-90. doi: 10.1111/j.1600-0528.1997.tb00941.x.

Reference Type: BACKGROUND

PMID: 9332805 (View on PubMed)

Other Identifiers

14-090

Identifier Type: -

Identifier Source: org_study_id