A Study of Rituximab Combined With Prednisone for the Initial Treatment of Chronic Graft Versus Host Disease (cGVHD)
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).
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Rituximab Combined With Prednisone for the Initial Treatment of Chronic Graft Versus Host Disease|
- 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 ] [ Designated as safety issue: No ]
- To determine the response rate to treatment, defined as complete response plus partial response (PR) for rituximab and prednisone [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To determine the rate of recurrent C-GVHD following initial therapy with rituximab and prednisone [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||May 2010|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Rituximab plus prednisone
Rituximab 375 mg/m2 IV weekly X 4 doses + Prednisone 1 mg/kg/d Treat 61 Patients
Rituximab 375 mg/m2 IV weekly X 4 doses + Prednisone 1 mg/kg/d
Other Name: Rituxan
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.
|Alberta Health Sciences - Tom Baker Cancer Centre|
|Calgary, Alberta, Canada, T1Y 6J4|
|Canada, British Columbia|
|Vancouver General Hospital|
|Vancouver, British Columbia, Canada, V5Z 1M9|
|Princess Maragaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||John Kuruvilla||University Health Network, Toronto|