Graft Versus Host DiseasePhase 2NCT00079183
Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment
A Phase 2 study testing sirolimus in people with Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2002to 10 Jun 2010
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of
- Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
- Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
- Absence of improvement after 3 months of primary treatment, or
- Continued need for treatment with prednisone at doses >= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen
- Patient or guardian able and willing to provide informed consent
Show all 9Show fewer
- Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)
- Stated willingness of the patient to comply with study procedures and reporting requirements
- Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements
Who cannot join
- Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
- Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
- Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
- Inability to tolerate oral medications
- Absolute neutrophil count (ANC) < 1500/uL
- Platelet count < 50,000/uL
Show all 9Show fewer
- Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
- Pregnancy
- Known history of hypersensitivity to sirolimus
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease
This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.
II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.
OUTLINE:
Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.
After completion of study treatment, patients are followed up periodically.
- Conditions
- Graft Versus Host Disease
- Being tested
- sirolimus
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called AY 22989, Rapamune, rapamycin, SLM
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center. Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Treatment Success
Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
Measured: Approximately 7 years
Number of Participants Experiencing Treatment Failure
Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.
Measured: Approximately 7 years
Number of Participants Needing Additional Systemic Therapy
Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.
Measured: Approximately 7 years
Number of Participants With Recurrent Malignancy
Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.
Measured: Approximately 7 years
Secondary outcomes (8)
Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
Measured: Approximately 7 years
Proportion With Infections Categorized by Organism
Measured: Approximately 7 years
Secondary Malignancies
Proportion of participants who developed at least one secondary malignancy by 7 years
Measured: Up to 7 years
Duration of Treatment With Prednisone
Measured: Approximately 7 years
Probability of Survival Without Recurrent Malignancy
Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.
Measured: Approximately 7 years
Probability of Overall Survival
Kaplan-Meier estimate assessed at 7 years
Measured: Approximately 7 years
Probability of Cumulative Incidence of Death Without Recurrent Malignancy
Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years.
Measured: Approximately 7 years
Probability of Cumulative Incidence of Recurrent Malignancy
Analyzed with death as a competing risk factor. Assessed at 7 years.
Measured: Approximately 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2004 (estimated)
- Study startApr 2002
- Primary completionJul 2009
- Study completion10 Jun 2010
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.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe 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
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Paul Carpenter, Fred Hutchinson Cancer Center
- Investigators
- Paul Carpenter, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00079183
- Sponsor's protocol ID
- 1706.00
- Other IDs
- NCI-2011-01817
- Status last verified
- May 2017
- First submitted
- 8 Mar 2004
- Last updated
- 20 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease
- ClinicalTrials.gov ID
- NCT00079183
- Acronym / sponsor ID
- 1706.00
- Conditions
- Graft Versus Host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2002
- Primary completion
- Jul 2009 (actual)
- Study completion
- 10 Jun 2010 (actual)
- First posted
- 10 Mar 2004 (estimated)
- Results
- Posted 12 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.
II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.
OUTLINE:
Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.
After completion of study treatment, patients are followed up periodically.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: sirolimusStudy participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of
- Patient or guardian able and willing to provide informed consent
- Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)
- Stated willingness of the patient to comply with study procedures and reporting requirements
- Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements
Key exclusion criteria (9 listed)
- Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
- Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
- Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
- Inability to tolerate oral medications
- Absolute neutrophil count (ANC) < 1500/uL
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: AY 22989, Rapamune, rapamycin, SLMGiven PO | Drug | Sirolimus |
Primary outcome
Number of Participants Experiencing Treatment Success
Time frame: Approximately 7 years
Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
Number of Participants Experiencing Treatment Failure
Time frame: Approximately 7 years
Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.
Number of Participants Needing Additional Systemic Therapy
Time frame: Approximately 7 years
Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.
Number of Participants With Recurrent Malignancy
Time frame: Approximately 7 years
Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.
8 secondary outcomes
Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
Time frame: Approximately 7 years
Proportion With Infections Categorized by Organism
Time frame: Approximately 7 years
Secondary Malignancies
Time frame: Up to 7 years
Duration of Treatment With Prednisone
Time frame: Approximately 7 years
Probability of Survival Without Recurrent Malignancy
Time frame: Approximately 7 years
Probability of Overall Survival
Time frame: Approximately 7 years
Probability of Cumulative Incidence of Death Without Recurrent Malignancy
Time frame: Approximately 7 years
Probability of Cumulative Incidence of Recurrent Malignancy
Time frame: Approximately 7 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Paul Carpenter principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sirolimus in people with Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 1 site in United States.
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 9 inclusion and 9 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: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 12 May 2017). 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?
Number of Participants Experiencing Treatment Success (time frame: Approximately 7 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jun 2017.