Chronic Graft-versus-Host-DiseasePhase 2NCT02123966

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

A Phase 2 study testing Sirolimus in people with Chronic Graft-versus-Host-Disease and Oral Mucosal Disease Due to Graft-versus-host Disease, run by Dana-Farber Cancer Institute at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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

Who is it for?: Ages 4 years and older
Conditions the study is for: Chronic Graft-versus-Host-Disease, Oral Mucosal Disease Due to Graft-versus-host Disease
What is being tested?: Sirolimus
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 2 sitesUnited States
Study dates: Jul 2014to May 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 4 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115

Other trials in United States

About this study

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

Read the 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
Being tested: Sirolimus
Keywords: Chronic Graft-versus-Host-Disease, Oral mucosal disease
Medical subject headings: Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SirolimusDrug
Also called Rapamune®

Study groups in NCT02123966
Study group	Role	What they receive
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. Receives: Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Oral health related quality of life will be assessed before and after topical sirolimus therapy using the 14-item Oral Health Impact Profile instrument that measures subject's perceptions of the impact of oral conditions on their well-being.
Measured: Pre treatment and after the 28 day (4 weeks) cycle of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2014May 2016

First posted28 Apr 2014 (estimated)
Study startJul 2014
Primary completionMay 2016
Study completionMay 2016

Why it stopped: Due to slow accrual, study team has decided to end the study early.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Chronic Graft-versus-Host-DiseaseStudies of the same condition, open and under way.
More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02123966
Sponsor's protocol ID: 14-090
Status last verified: Jun 2018
First submitted: 23 Apr 2014
Last updated: 24 Jul 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 25529383
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.
PubMed 9332805

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label Phase II Trial of Topical Sirolimus for the Treatment of Refractory Oral Chronic Graft-versus-Host-Disease
ClinicalTrials.gov ID: NCT02123966
Acronym / sponsor ID: 14-090
Conditions: Chronic Graft-versus-Host-Disease, Oral Mucosal Disease Due to Graft-versus-host Disease
Keywords: Chronic Graft-versus-Host-Disease, Oral mucosal disease
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Due to slow accrual, study team has decided to end the study early.
Enrolment: 10 participants (actual)
Lead sponsor: Dana-Farber Cancer InstituteUniversity, hospital or other
Study start: Jul 2014 (actual)
Primary completion: May 2016 (actual)
Study completion: May 2016 (actual)
First posted: 28 Apr 2014 (estimated)
Results: Posted 24 Jul 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Topical Sirolimus + Steroid	Experimental	Drug: SirolimusA 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.

Who may qualify

Ages: 4 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SirolimusAlso: Rapamune®	Drug	Topical Sirolimus + Steroid

Primary outcome

Percentage of Participants With a Subjective Sensitivity Score Response
Time frame: Pre treatment and after the 28 day (4 weeks) cycle of treatment
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.

1 secondary outcome

Change Pre-to-post Treatment in Oral Health Impact Profile Assessment
Time frame: Pre treatment and after the 28 day (4 weeks) cycle of treatment

Results and safety

Results posted to the registry on 24 Jul 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Topical Sirolimus + Steroid	10	9

Primary outcome: Percentage of Participants With a Subjective Sensitivity Score Response

Time frame: Pre treatment and after the 28 day (4 weeks) cycle of treatment. Number (90% Confidence Interval). Unit: percentage of participants

Measure	Topical Sirolimus + Steroid n = 10
Value	20 (3.7 to 50.7)

Population analysed: The analysis population is comprised of all treated participants.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were evaluated at the clinical exam at completion of protocol treatment, up to day 33.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sirolimus	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Limitations and caveats (from the sponsor): This study was terminated early due to weak accrual.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25529383Jagasia 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.
Background: PubMed 9332805Slade 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nathaniel S Treister, DMD, DMSc principal investigator

Brigham and Women's Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With a Subjective Sensitivity Score Response (time frame: Pre treatment and after the 28 day (4 weeks) cycle of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02123966, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2018.