Graft Versus Host DiseasePhase 2NCT01066598
A Study of Rituximab Combined With Prednisone for the Initial Treatment of Chronic Graft Versus Host Disease (cGVHD)
A Phase 2 study testing Rituximab in people with Graft Versus Host Disease, run by University Health Network, Toronto at 3 sites in Canada.
Trial summary
The purpose of this study is to determine the efficacy of the combination of rituximab and prednisone as initial therapy for chronic graft-versus-host disease (C-GVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 3 sitesCanada
- Study dates
- May 2010to Aug 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Previously untreated symptomatic classical C-GVHD (with prior allogeneic stem cell transplant) requiring systemic therapy (defined as per NIH Consensus: a)At least 3 sites of organ involvement or individual organ score of at least 2, b)Patients on agents for GVHD prophylaxis (such as therapeutic dose or tapering cyclosporine A or tacrolimus) or patients that have received therapy for acute GVHD prior to enrollment are eligible
- Patients must be 18 years of age or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events response assessment and follow-up.
- Patient must be willing and able to complete the GVHD questionnaire
- For patients that have been started on prednisone therapy for cGVHD but otherwise meet all of the eligibility criteria, registration into this trial must occur no later than 14 days from the start of prednisone therapy.
Who cannot join
- Uncontrolled infection at the time of study enrollment
- Recurrent malignancy at the time of study enrollment
- Previous systemic therapy for C-GVHD, a)Patients on agents for GVHD prophylaxis (such as therapeutic dose or tapering cyclosporine A or tacrolimus) or patients that have received therapy for acute GVHD prior to enrollment are eligible. b)Patients who have been restarted on full doses of agents used for GVHD prophylaxis (ie. cyclosporine A or tacrolimus) after these have tapered or discontinued are not eligible
- Inability to tolerate prednisone (includes pre-existing myopathy, diabetes with poor glycemic control, uncontrolled hypertension or fluid retention) or rituximab
- Usage of additional concurrent agents which could treat C-GVHD (ie. chemotherapeutic agents - cyclophosphamide, methotrexate or other immunosuppressive agents). Patients may be continued on stable or tapering dose of GVHD prophylaxis agents such as cyclosporine or tacrolimus, but must be tapered off by first study treatment
- The administration of anticancer therapies or other investigational agents is not permitted. Use of hematopoietic colony stimulating factors to manage blood counts is allowed.
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- Sexually active males and females of childbearing potential unwilling to practice contraception during the study. Patients of childbearing potential must be willing to use a reliable method of birth control (i.e. double barrier method).
- Women of childbearing potential with either a positive or no pregnancy test at baseline or lactating. Postmenopausal women must have been amenorrheic for at least 12 months or surgically sterile to be considered of non-childbearing potential.
- Patients with immune deficiency are at increased risk of lethal infections. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions.
- Patients with active hepatitis B are excluded
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Alberta Health Sciences - Tom Baker Cancer Centre
Calgary, Alberta, T1Y 6J4
Princess Maragaret Hospital
Toronto, Ontario, M5G 2M9
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: A Phase II Study of Rituximab Combined With Prednisone for the Initial Treatment of Chronic Graft Versus Host Disease
The purpose of this study is to determine the efficacy of the combination of rituximab and prednisone as initial therapy for chronic graft-versus-host disease (C-GVHD).
Read the detailed description
Host antigen-presenting cells (APC) have an important role in the pathogenesis of chronic graft-versus-host disease (C-GVHD). B cell antigen-presenting cells may also be important in activating T cells in vivo. In a murine leukemia model, B cells have been shown to be important APCs in T cell responses. Rates of C-GVHD were shown to lower in a B cell deficient murine model when compared to mice that received rabbit immunoglobulin, and the rate of C-GVHD was even lower if grafts were depleted of B cells. It would appear that B cells have an important role as APCs in the pathogenesis of C-GVHD.
The chimeric anti-CD20 antibody Rituximab has been demonstrated to have activity in steroid-refractory graft versus host disease in a few small retrospective studies. Previous evidence in indolent lymphoma has demonstrated that Rituximab is a potent B-cell depleting agent. These observations suggest that B-cell depletion in graft versus host disease may be an effective therapy. Rituximab is currently being evaluated in two separate phase II studies currently enrolling patients who have had an allogeneic stem cell transplant (allo-SCT) or have developed GVHD.
The Dana Farber BMT program has recently published a phase II study examining the safety and effectiveness of rituximab monotherapy in the setting of steroid-refractory GVHD. Rituximab was administered weekly at the standard dose of 375 mg/m2. The clinical response rate was 70% and responses were limited to patients with cutaneous and musculoskeletal manifestations of C-GVHD. Median corticosteroid doses improved from 40 mg/day to 10 mg/day. The BMT program at Stanford is enrolling patients in a phase II study examining the impact of 4 weekly doses of 375 mg/m2 of Rituximab given starting on day +56 following allo-SCT in patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) in an attempt to prevent the development of subsequent GVHD.
These two studies will provide important phase II data regarding the safety and efficacy of Rituximab in the prevention of GVHD and the treatment of steroid-refractory GVHD. Another area of interest would be the initial treatment of GVHD. Although there is no universally recognized standard of care, corticosteroids form the backbone of treatment for GVHD and are either given as single agents or part of a combination therapy strategy with Cyclosporine A (CsA), Tacrolimus (FK506) or mycophenolate mofetil (MMF).
We propose a phase II study of rituximab in combination with prednisone as primary therapy for C-GVHD.
- Conditions
- Graft Versus Host Disease
- Being tested
- Rituximab
- Keywords
- graft versus host disease, chronic graft versus host disease, cGVHD
- Medical subject headings
- Graft vs Host Disease, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
Rituximab 375 mg/m2 IV weekly X 4 doses + Prednisone 1 mg/kg/d
| Study group | Role | What they receive |
|---|---|---|
| Rituximab plus prednisone | Experimental | Rituximab 375 mg/m2 IV weekly X 4 doses + Prednisone 1 mg/kg/d Treat 61 Patients Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The efficacy of the combination of rituximab and prednisone as initial therapy for C-GVHD, which is defined as discontinuation of immunosuppressive therapy at 12 months with resolution of reversible manifestations of C-GVHD
Measured: 12 months
Secondary outcomes (5)
To determine the response rate to treatment, defined as complete response plus partial response (PR) for rituximab and prednisone
Measured: 3 years
To determine the rate of recurrent C-GVHD following initial therapy with rituximab and prednisone
Measured: 3 years
To determine the relapse rate of the underlying malignancy for which the allo-SCT was performed from time of study registration after treatment with rituximab and prednisone
Measured: 3 years
To determine the rate of infection requiring treatment with anti-bacterial, anti-fungal or anti-viral therapy from time of study registration after treatment with rituximab and prednisone
Measured: 3 years
To determine overall survival of treated patients from time of study registration to a maximum of 3 years following study registration for patients receiving rituximab and prednisone
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2010 (estimated)
- Study startMay 2010
- Primary completionAug 2011
- Study completionAug 2011
Why it stopped: Poor Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Investigators
- John Kuruvilla, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01066598
- Sponsor's protocol ID
- OZM-009 (GVHD-R01)
- Status last verified
- Aug 2011
- First submitted
- 8 Feb 2010
- Last updated
- 7 Sep 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Rituximab Combined With Prednisone for the Initial Treatment of Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT01066598
- Acronym / sponsor ID
- OZM-009 (GVHD-R01)
- Conditions
- Graft Versus Host Disease
- Keywords
- graft versus host disease, chronic graft versus host disease, cGVHD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor Accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- May 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 10 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the efficacy of the combination of rituximab and prednisone as initial therapy for chronic graft-versus-host disease (C-GVHD).
Detailed description
Host antigen-presenting cells (APC) have an important role in the pathogenesis of chronic graft-versus-host disease (C-GVHD). B cell antigen-presenting cells may also be important in activating T cells in vivo. In a murine leukemia model, B cells have been shown to be important APCs in T cell responses. Rates of C-GVHD were shown to lower in a B cell deficient murine model when compared to mice that received rabbit immunoglobulin, and the rate of C-GVHD was even lower if grafts were depleted of B cells. It would appear that B cells have an important role as APCs in the pathogenesis of C-GVHD.
The chimeric anti-CD20 antibody Rituximab has been demonstrated to have activity in steroid-refractory graft versus host disease in a few small retrospective studies. Previous evidence in indolent lymphoma has demonstrated that Rituximab is a potent B-cell depleting agent. These observations suggest that B-cell depletion in graft versus host disease may be an effective therapy. Rituximab is currently being evaluated in two separate phase II studies currently enrolling patients who have had an allogeneic stem cell transplant (allo-SCT) or have developed GVHD.
The Dana Farber BMT program has recently published a phase II study examining the safety and effectiveness of rituximab monotherapy in the setting of steroid-refractory GVHD. Rituximab was administered weekly at the standard dose of 375 mg/m2. The clinical response rate was 70% and responses were limited to patients with cutaneous and musculoskeletal manifestations of C-GVHD. Median corticosteroid doses improved from 40 mg/day to 10 mg/day. The BMT program at Stanford is enrolling patients in a phase II study examining the impact of 4 weekly doses of 375 mg/m2 of Rituximab given starting on day +56 following allo-SCT in patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) in an attempt to prevent the development of subsequent GVHD.
These two studies will provide important phase II data regarding the safety and efficacy of Rituximab in the prevention of GVHD and the treatment of steroid-refractory GVHD. Another area of interest would be the initial treatment of GVHD. Although there is no universally recognized standard of care, corticosteroids form the backbone of treatment for GVHD and are either given as single agents or part of a combination therapy strategy with Cyclosporine A (CsA), Tacrolimus (FK506) or mycophenolate mofetil (MMF).
We propose a phase II study of rituximab in combination with prednisone as primary therapy for C-GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab plus prednisone | Experimental | Drug: RituximabRituximab 375 mg/m2 IV weekly X 4 doses + Prednisone 1 mg/kg/d Treat 61 Patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Previously untreated symptomatic classical C-GVHD (with prior allogeneic stem cell transplant) requiring systemic therapy (defined as per NIH Consensus: a)At least 3 sites of organ involvement or individual organ score of at least 2, b)Patients on agents for GVHD prophylaxis (such as therapeutic dose or tapering cyclosporine A or tacrolimus) or patients that have received therapy for acute GVHD prior to enrollment are eligible
- Patients must be 18 years of age or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events response assessment and follow-up.
- Patient must be willing and able to complete the GVHD questionnaire
Key exclusion criteria (10 listed)
- Uncontrolled infection at the time of study enrollment
- Recurrent malignancy at the time of study enrollment
- Previous systemic therapy for C-GVHD, a)Patients on agents for GVHD prophylaxis (such as therapeutic dose or tapering cyclosporine A or tacrolimus) or patients that have received therapy for acute GVHD prior to enrollment are eligible. b)Patients who have been restarted on full doses of agents used for GVHD prophylaxis (ie. cyclosporine A or tacrolimus) after these have tapered or discontinued are not eligible
- Inability to tolerate prednisone (includes pre-existing myopathy, diabetes with poor glycemic control, uncontrolled hypertension or fluid retention) or rituximab
- Usage of additional concurrent agents which could treat C-GVHD (ie. chemotherapeutic agents - cyclophosphamide, methotrexate or other immunosuppressive agents). Patients may be continued on stable or tapering dose of GVHD prophylaxis agents such as cyclosporine or tacrolimus, but must be tapered off by first study treatment
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 |
|---|---|---|
| RituximabAlso: RituxanRituximab 375 mg/m2 IV weekly X 4 doses + Prednisone 1 mg/kg/d | Drug | Rituximab plus prednisone |
Primary outcome
The efficacy of the combination of rituximab and prednisone as initial therapy for C-GVHD, which is defined as discontinuation of immunosuppressive therapy at 12 months with resolution of reversible manifestations of C-GVHD
Time frame: 12 months
5 secondary outcomes
To determine the response rate to treatment, defined as complete response plus partial response (PR) for rituximab and prednisone
Time frame: 3 years
To determine the rate of recurrent C-GVHD following initial therapy with rituximab and prednisone
Time frame: 3 years
To determine the relapse rate of the underlying malignancy for which the allo-SCT was performed from time of study registration after treatment with rituximab and prednisone
Time frame: 3 years
To determine the rate of infection requiring treatment with anti-bacterial, anti-fungal or anti-viral therapy from time of study registration after treatment with rituximab and prednisone
Time frame: 3 years
To determine overall survival of treated patients from time of study registration to a maximum of 3 years following study registration for patients receiving rituximab and prednisone
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Poor Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2011.
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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.
John Kuruvilla principal investigator
University Health Network, Toronto
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Graft Versus Host Disease, run by University Health Network, Toronto at 3 sites in Canada.
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 6 inclusion and 10 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 7 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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?
The study was stopped early (reason given: Poor Accrual). Results are not available in the source record.
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 efficacy of the combination of rituximab and prednisone as initial therapy for C-GVHD, which is defined as discontinuation of immunosuppressive therapy at 12 months with resolution of reversible manifestations of C-GVHD (time frame: 12 months). 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 7 Sep 2011.