Acute Graft Versus Host DiseasePhase 3NCT00726375
The Use of Etanercept Enbrel as Sole Treatment for Grade I Acute Graft Versus Host Disease
A Phase 3 study testing Etanercept (Enbrel) in people with Acute Graft Versus Host Disease, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This is a clinical trial to see if treatment with etanercept for early skin graft-versus-host disease (GVHD) can effectively treat and prevent progression of the disease without using high dose steroids. GVHD is a common complication following a bone marrow transplant from another donor. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Graft Versus Host Disease
- What is being tested?
- Etanercept (Enbrel)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Sep 2014
- Phase
- Phase 3
- 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
- Patient must have undergone HCT (donor cells from any source) with either a myeloablative or nonmyeloablative preparative regimen.
- Patient may be any age.
- Patient must have biopsy-proven Grade I acute GVHD (Appendix A). Biopsy report does not have to be back from Pathology prior to enrollment. Patients whose biopsy for GVHD identifies pathology inconsistent with GVHD will be removed from the study and replaced. However, because GVHD is a clinical diagnosis, biopsies which are non-diagnostic or do not show a clear non-GVHD etiology will not be cause to remove the patient from the study.
Who cannot join
- Patients who are pregnant (positive urine or serum test) or nursing.
- Active infections which are unresponsive to antibiotics (> 2 consecutive [at least 24 hours apart], positive blood cultures after initiation of treatment).
- Allergic or otherwise undesirable reaction to etanercept.
- Use of any oral or intravenous steroids at any previous time for GVHD treatment. Prior use of steroid therapy (i.e. hydrocortisone) as pre-medication for transfusions is permissible. Prior use of topical steroids is allowed.
- Use of etanercept for any other purpose.
- Noncompliance with medications.
- Grade II-IV GVHD (history of or at time of study entry).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of Etanercept (Enbrel) as Sole Treatment for Grade I Acute Graft Versus Host Disease
This is a clinical trial to see if treatment with etanercept for early skin graft-versus-host disease (GVHD) can effectively treat and prevent progression of the disease without using high dose steroids.
GVHD is a common complication following a bone marrow transplant from another donor. GVHD occurs after transplant, when the donor's blood cells (called lymphocytes) recognize parts of your body, such as the skin, as foreign. A certain chemical, called Tumor Necrosis Factor, or TNF, also causes damage to the skin. The main effect on the skin is a red rash, when the skin GVHD is mild, but in more severe forms the skin can blister.
Read more
We have been studying GVHD at the University of Michigan for the past decade. We know that high levels of TNF makes GVHD worse. Our research has shown that adding an anti-TNF drug (called etanercept or Enbrel®) to the standard GVHD treatment of high dose steroids leads to improvement in the GVHD in twice as many patients compared to when steroids alone are used. It is now standard practice at the University of Michigan and many other centers to treat GVHD with both steroids and etanercept.
The management of early skin GVHD for most patients involves treatment with steroids, given both as a cream and by either the mouth (in pills) or IV. Early skin GVHD is also called grade I GVHD, which means the skin rash covers less than half of the body. Steroid treatment can be effective; however, it also causes many complications such as an increased risk of infection, weight gain, stomach ulcers, muscle weakness and bone damage, among many others. We have developed this study to test whether starting treatment with etanercept and steroid creams alone can treat the GVHD without requiring the use of high dose steroids. The goal is to avoid the complications that come with high dose oral or IV steroid treatment. The high dose steroid treatment would only begin if your GVHD got worse.
- Conditions
- Acute Graft Versus Host Disease
- Being tested
- Etanercept (Enbrel)
- Keywords
- (GVHD)
- 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.
Etanercept (Enbrel)Drug
Etanercept will begin within 72 hours of the diagnosis of Grade I acute GVHD and after consent for this study. Subjects receive eight doses of etanercept over four weeks. All doses will be administered by SQ injection. All subsequent doses will be given as subcutaneous injections into the skin. Injections will be given twice weekly with at least one day in between injections. The injections can be given in clinic, in the hospital, or self administered injections.
| Study group | Role | What they receive |
|---|---|---|
| Etanercept | Experimental | a maximum of 8 SQ doses of 'Etanercept (Enbrel) at 0.4mg/kg per dose up to a maximum of 25 mg per dose Receives: Drug: Etanercept (Enbrel) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment
We hypothesized that treatment of grade 1 acute GVHD (Graft Versus Host Disease) with etanercept would reduce the proportion of patients who progressed to grade 2 to 4 acute GVHD within 4 weeks of diagnosis from 58%, historically observed at our institution, to 38%.
Measured: 28 days
Secondary outcomes (1)
The Number of Patients in Complete Remission (CR) at Four Weeks.
Estimate the proportion of patients in complete remission (CR) at four weeks who remain alive and never require additional therapy four weeks after the last dose of etanercept.
Complete remission is defined as the resolution of all manifestations of GVHD (Graft Versus Host Disease) within the first four weeks of treatment. All organs must have a Grade 0.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2008 (estimated)
- Study startMay 2008
- Primary completionJul 2013
- Study completionSep 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sung Choi, MD, Principal investigator, The University of Michigan Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00726375
- Sponsor's protocol ID
- UMCC 2007.139
- Other IDs
- HUM 17897
- Status last verified
- Dec 2015
- First submitted
- 28 Jul 2008
- Last updated
- 5 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gatza E, Braun T, Levine JE, Ferrara JL, Zhao S, Wang T, Chang L, Harris A, Pawarode A, Kitko C, Magenau JM, Yanik GA, Couriel DR, Goldstein S, Connelly J, Reddy P, Paczesny S, Choi SW. Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014 Sep;20(9):1426-34. doi: 10.1016/j.bbmt.2014.05.023. Epub 2014 Jun 2.
PubMed 24892263
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Etanercept (Enbrel) as Sole Treatment for Grade I Acute Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT00726375
- Acronym / sponsor ID
- UMCC 2007.139
- Conditions
- Acute Graft Versus Host Disease
- Keywords
- (GVHD)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Jul 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 31 Jul 2008 (estimated)
- Results
- Posted 4 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a clinical trial to see if treatment with etanercept for early skin graft-versus-host disease (GVHD) can effectively treat and prevent progression of the disease without using high dose steroids.
GVHD is a common complication following a bone marrow transplant from another donor. GVHD occurs after transplant, when the donor's blood cells (called lymphocytes) recognize parts of your body, such as the skin, as foreign. A certain chemical, called Tumor Necrosis Factor, or TNF, also causes damage to the skin. The main effect on the skin is a red rash, when the skin GVHD is mild, but in more severe forms the skin can blister.
We have been studying GVHD at the University of Michigan for the past decade. We know that high levels of TNF makes GVHD worse. Our research has shown that adding an anti-TNF drug (called etanercept or Enbrel®) to the standard GVHD treatment of high dose steroids leads to improvement in the GVHD in twice as many patients compared to when steroids alone are used. It is now standard practice at the University of Michigan and many other centers to treat GVHD with both steroids and etanercept.
The management of early skin GVHD for most patients involves treatment with steroids, given both as a cream and by either the mouth (in pills) or IV. Early skin GVHD is also called grade I GVHD, which means the skin rash covers less than half of the body. Steroid treatment can be effective; however, it also causes many complications such as an increased risk of infection, weight gain, stomach ulcers, muscle weakness and bone damage, among many others. We have developed this study to test whether starting treatment with etanercept and steroid creams alone can treat the GVHD without requiring the use of high dose steroids. The goal is to avoid the complications that come with high dose oral or IV steroid treatment. The high dose steroid treatment would only begin if your GVHD got worse.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etanercept | Experimental | Drug: Etanercept (Enbrel)a maximum of 8 SQ doses of 'Etanercept (Enbrel) at 0.4mg/kg per dose up to a maximum of 25 mg per dose |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patient must have undergone HCT (donor cells from any source) with either a myeloablative or nonmyeloablative preparative regimen.
- Patient may be any age.
- Patient must have biopsy-proven Grade I acute GVHD (Appendix A). Biopsy report does not have to be back from Pathology prior to enrollment. Patients whose biopsy for GVHD identifies pathology inconsistent with GVHD will be removed from the study and replaced. However, because GVHD is a clinical diagnosis, biopsies which are non-diagnostic or do not show a clear non-GVHD etiology will not be cause to remove the patient from the study.
Key exclusion criteria (7 listed)
- Patients who are pregnant (positive urine or serum test) or nursing.
- Active infections which are unresponsive to antibiotics (> 2 consecutive [at least 24 hours apart], positive blood cultures after initiation of treatment).
- Allergic or otherwise undesirable reaction to etanercept.
- Use of any oral or intravenous steroids at any previous time for GVHD treatment. Prior use of steroid therapy (i.e. hydrocortisone) as pre-medication for transfusions is permissible. Prior use of topical steroids is allowed.
- Use of etanercept for any other purpose.
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 |
|---|---|---|
| Etanercept (Enbrel)Etanercept will begin within 72 hours of the diagnosis of Grade I acute GVHD and after consent for this study. Subjects receive eight doses of etanercept over four weeks. All doses will be administered by SQ injection. All subsequent doses will be given as subcutaneous injections into the skin. Injections will be given twice weekly with at least one day in between injections. The injections can be given in clinic, in the hospital, or self administered injections. | Drug | Etanercept |
Primary outcome
The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment
Time frame: 28 days
We hypothesized that treatment of grade 1 acute GVHD (Graft Versus Host Disease) with etanercept would reduce the proportion of patients who progressed to grade 2 to 4 acute GVHD within 4 weeks of diagnosis from 58%, historically observed at our institution, to 38%.
1 secondary outcome
The Number of Patients in Complete Remission (CR) at Four Weeks.
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24892263Gatza E, Braun T, Levine JE, Ferrara JL, Zhao S, Wang T, Chang L, Harris A, Pawarode A, Kitko C, Magenau JM, Yanik GA, Couriel DR, Goldstein S, Connelly J, Reddy P, Paczesny S, Choi SW. Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014 Sep;20(9):1426-34. doi: 10.1016/j.bbmt.2014.05.023. Epub 2014 Jun 2.
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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.
Sung Choi, MD principal investigator
The University of Michigan Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etanercept (Enbrel) in people with Acute Graft Versus Host Disease, run by University of Michigan Rogel 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 3 inclusion and 7 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 5 Jan 2016. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 4 Aug 2014). 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?
The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment (time frame: 28 days). 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 NCT00726375, which also lists 1 linked publication.
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 5 Jan 2016.