Acute Graft Versus Host DiseasePhase 1/2NCT01475162
Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease
A Phase 1/2 study testing Tocilizumab in people with Acute Graft Versus Host Disease, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This trial designed to evaluate the toxicity and efficacy of tocilizumab in the treatment of steroid refractory acute graft versus host disease (GVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Graft Versus Host Disease
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2011to 29 Sep 2018
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients age 18 and older who underwent an allogeneic hematopoietic stem cell transplantation.
- Patients are required to have biopsy proven GVHD.
- Patients must have active acute GVHD requiring systemic immune suppressive therapy and that failed or did not respond to first line of therapy.
- First line therapy needs to be a minimum of corticosteroids, methylprednisolone of 1.6mg/kg/day or prednisone of 2mg/kg/day, alone or combined to other agent.
- Failure of GVHD therapy is defined as flare of signs and symptoms of acute GVHD or progression of GVHD grade after at least 72 hours from starting therapy.
- No response to GVHD treatment (corticosteroids ± other agent) after a minimum of 7 days of treatment.
- Patient must be able to give informed consent.
Who cannot join
- Intolerance or allergy to Tocilizumab
- Active uncontrolled infection requiring ongoing treatment with antifungals, antibiotics or anti-viral drugs.
- Relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
- Liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3x upper limit of normal.
- Patients with severe sinusoidal obstruction syndrome who in the judgment of the treating physician are not expected to have normalized bilirubin by day 56 after enrollment.
- Serum bilirubin > 2x upper limit of normal.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert Hospital/Medical College of Wisconsin-Clinical Cancer Center
Milwaukee, Wisconsin, 53226
About this study
Official title: Phase I-II Study Using Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease
This trial designed to evaluate the toxicity and efficacy of tocilizumab in the treatment of steroid refractory acute graft versus host disease (GVHD).
Read the detailed description
Patients who underwent an allogeneic hematopoietic stem cell transplantation, with biopsy proven GVHD, active acute GVHD requiring systemic immune suppressive therapy and that failed or did not respond to first line of therapy (corticosteroids ± other agent).
Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks. Subsequent discontinuation of Tocilizumab will occur once patients are off other immune suppressive medications (including extracorporeal photopheresis, ECP) or are receiving sub therapeutic levels of immunosuppression (i.e., Tacrolimus (FK) levels <5 ng/mL) or prednisone dose <20 mg/day (or equivalent) and are free of acute GVHD signs or symptoms for at least one month.
Patients who fulfill criteria of progression of GVHD not in the setting of immunosuppressive taper, no response of GVHD or require initiation of other immune suppressive treatment for GVHD will have Tocilizumab discontinued.
Tocilizumab shall be discontinued and not re-instituted if any one of the following criteria is met. The patient will be taken off study drug therapy at that point, but still followed for primary and secondary study endpoints. A response assessment will be made at the time of therapy discontinuation and at subsequent defined study endpoints. The patient will not be replaced on study. Follow-up data will be required unless consent for data collection is withdrawn:
- Additional systemic GVHD therapy is added for disease progression or non-response
- Steroid dose is escalated to ≥ 2.5 mg/kg/day of prednisone (or methylprednisolone equivalent of 2 mg/kg/day) for GVHD progression or no response
- Development of toxicity that requires withholding of study medication for more then 14 days
- Conditions
- Acute Graft Versus Host Disease
- Being tested
- Tocilizumab
- Keywords
- acute Graft versus Host Disease (aGVHD), steroid refractory acute Graft versus Host Disease (aGVHD), chronic Graft versus Host Disease (cGVHD), corticosteroids, allogeneic hematopoietic stem cell transplantation
- 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.
TocilizumabDrug
Also called Actemra
Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | Drug: Tocilizumab
Other Names:
Actemra
Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response. Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Achieving Complete or Partial Response at Day 56 After Administration of Tocilizumab
Number of subjects achieving Center for International Blood and Marrow Transplant Research (CIBMTR) score of 0 (complete response); or achieving improvement in one or more organs involved in GVHD without progression in other organs (partial response). CIBMTR score of 0 means no evidence of rash or diarrhea and bilirubin less than 2.0 mg/dl. CIBMTR score of 4 means rash with bullae desquamation, lower gastrointestinal diarrhea more than 1,500 ml, and bilirubin greater than 15.1 mg/dl. Higher score means worse disease.
Measured: Day 56
Secondary outcomes (7)
Number of Patients With Partial, Mixed or no GVHD Responses
Number of subjects achieving improvement in one or more organs involved in GVHD with or without deterioration in another organ (mixed or partial response, respectively); or having received additional immune suppressive therapy (no response).
Measured: Day 56
GVHD Flares
Number of subjects exhibiting any progression requiring re-escalation of steroid dosing or initiation of additional topical or systemic therapy after achieving an initial complete or partial response prior to Day 90.
Measured: Day 90
Discontinuation of Immunosuppression
Number of subjects for whom immunosuppressive therapy (corticosteroid, cyclosporine, tacrolimus, sirolimus, etc.) was discontinued. This will be evaluated at Day 56, Day 180 and Day 365.
Measured: Day 56, Day 180 and Day 365
Overall Survival
Number of subjects alive at one year.
Measured: 1 year
Number of Subjects Experiencing at Least One Serious Adverse Event or Grade 3 Non-serious Adverse Event
Number of subjects experiencing at least one serious adverse event or adverse event of CTCAE grade 3, 4, or 5 at Day 56 following the initiation of tocilizumab therapy.
Measured: Day 56
Disease-free Survival
Number of subjects alive and not experiencing GVHD signs or symptoms at 6 and 12 months. At the six month time point, seven subjects had expired. At the 12 month time point, 10 subjects had expired.
Measured: 6 and 12 months
Non-relapse Mortality
Number of subjects expiring from causes other than relapse of GVHD disease.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2011 (estimated)
- Study start8 Aug 2011
- Primary completion17 Feb 2016
- Study completion29 Sep 2018
Why it stopped: The DSMB felt the risks of the study now outweighed the potential benefits.
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 Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William R. Drobyski, MD, Medical College of Wisconsin
- Investigators
- William R Drobyski, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01475162
- Sponsor's protocol ID
- MCW-PRO15904
- Status last verified
- Jan 2020
- First submitted
- 16 Nov 2011
- Last updated
- 17 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study Using Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease
- ClinicalTrials.gov ID
- NCT01475162
- Acronym / sponsor ID
- MCW-PRO15904
- Conditions
- Acute Graft Versus Host Disease
- Keywords
- acute Graft versus Host Disease (aGVHD), steroid refractory acute Graft versus Host Disease (aGVHD), chronic Graft versus Host Disease (cGVHD), corticosteroids, allogeneic hematopoietic stem cell transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The DSMB felt the risks of the study now outweighed the potential benefits.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 8 Aug 2011 (actual)
- Primary completion
- 17 Feb 2016 (actual)
- Study completion
- 29 Sep 2018 (actual)
- First posted
- 21 Nov 2011 (estimated)
- Results
- Posted 31 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial designed to evaluate the toxicity and efficacy of tocilizumab in the treatment of steroid refractory acute graft versus host disease (GVHD).
Detailed description
Patients who underwent an allogeneic hematopoietic stem cell transplantation, with biopsy proven GVHD, active acute GVHD requiring systemic immune suppressive therapy and that failed or did not respond to first line of therapy (corticosteroids ± other agent).
Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks. Subsequent discontinuation of Tocilizumab will occur once patients are off other immune suppressive medications (including extracorporeal photopheresis, ECP) or are receiving sub therapeutic levels of immunosuppression (i.e., Tacrolimus (FK) levels <5 ng/mL) or prednisone dose <20 mg/day (or equivalent) and are free of acute GVHD signs or symptoms for at least one month.
Patients who fulfill criteria of progression of GVHD not in the setting of immunosuppressive taper, no response of GVHD or require initiation of other immune suppressive treatment for GVHD will have Tocilizumab discontinued.
Tocilizumab shall be discontinued and not re-instituted if any one of the following criteria is met. The patient will be taken off study drug therapy at that point, but still followed for primary and secondary study endpoints. A response assessment will be made at the time of therapy discontinuation and at subsequent defined study endpoints. The patient will not be replaced on study. Follow-up data will be required unless consent for data collection is withdrawn:
- Additional systemic GVHD therapy is added for disease progression or non-response
- Steroid dose is escalated to ≥ 2.5 mg/kg/day of prednisone (or methylprednisolone equivalent of 2 mg/kg/day) for GVHD progression or no response
- Development of toxicity that requires withholding of study medication for more then 14 days
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: TocilizumabDrug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients age 18 and older who underwent an allogeneic hematopoietic stem cell transplantation.
- Patients are required to have biopsy proven GVHD.
- Patients must have active acute GVHD requiring systemic immune suppressive therapy and that failed or did not respond to first line of therapy.
- Patient must be able to give informed consent.
Key exclusion criteria (6 listed)
- Intolerance or allergy to Tocilizumab
- Active uncontrolled infection requiring ongoing treatment with antifungals, antibiotics or anti-viral drugs.
- Relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
- Liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3x upper limit of normal.
- Patients with severe sinusoidal obstruction syndrome who in the judgment of the treating physician are not expected to have normalized bilirubin by day 56 after enrollment.
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 |
|---|---|---|
| TocilizumabAlso: ActemraTocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response. | Drug | Tocilizumab |
Primary outcome
Number of Subjects Achieving Complete or Partial Response at Day 56 After Administration of Tocilizumab
Time frame: Day 56
Number of subjects achieving Center for International Blood and Marrow Transplant Research (CIBMTR) score of 0 (complete response); or achieving improvement in one or more organs involved in GVHD without progression in other organs (partial response). CIBMTR score of 0 means no evidence of rash or diarrhea and bilirubin less than 2.0 mg/dl. CIBMTR score of 4 means rash with bullae desquamation, lower gastrointestinal diarrhea more than 1,500 ml, and bilirubin greater than 15.1 mg/dl. Higher score means worse disease.
7 secondary outcomes
Number of Patients With Partial, Mixed or no GVHD Responses
Time frame: Day 56
GVHD Flares
Time frame: Day 90
Discontinuation of Immunosuppression
Time frame: Day 56, Day 180 and Day 365
Overall Survival
Time frame: 1 year
Number of Subjects Experiencing at Least One Serious Adverse Event or Grade 3 Non-serious Adverse Event
Time frame: Day 56
Disease-free Survival
Time frame: 6 and 12 months
Non-relapse Mortality
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- 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.
William R Drobyski, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tocilizumab in people with Acute Graft Versus Host Disease, run by Medical College of Wisconsin 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 7 inclusion and 6 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 17 Feb 2020. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 31 Jan 2020). 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 Subjects Achieving Complete or Partial Response at Day 56 After Administration of Tocilizumab (time frame: Day 56). 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 17 Feb 2020; AzTrials last refreshed its copy on 7 Nov 2026.