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

NCT02123966 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 14-090
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

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

Keywords

Chronic Graft-versus-Host-Disease; Oral mucosal disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Subjective Sensitivity Score Response

  The sensitivity score is one question on a self-reported assessment tool from the NIH consensus documents. The question asks: "Your mouth sensitivity at its WORST" with a score 0-10, 10 being the worst. Response was defined as a 3 point reduction in sensitivity score from pre-to-post treatment.

  Pre treatment and after the 28 day (4 weeks) cycle of treatment

Secondary Outcomes (1)

• Change Pre-to-post Treatment in Oral Health Impact Profile Assessment

  Pre treatment and after the 28 day (4 weeks) cycle of treatment

Study Arms (1)

Topical Sirolimus + Steroid

EXPERIMENTAL

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.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Also known as: Rapamune®

Topical Sirolimus + Steroid

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• 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.

  PMID: 25529383 BACKGROUND

• 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.

  PMID: 9332805 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

This study was terminated early due to weak accrual.

Results Point of Contact

• Title: Nathaniel S. Treister, DMD, DMSc
• Organization: Dana-Farber Cancer Institute

ntreister@partners.org

617-632-2806

Study Officials

• Nathaniel S Treister, DMD, DMSc

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: April 28, 2014
• Study Start: July 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: July 24, 2018
• Results First Posted: July 24, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)