Mycophenolate Mofetil (MMF) for Treatment of Chronic Graft-versus-host Disease (GVHD)
RATIONALE: Mycophenolate mofetil added to immunosuppressive treatment regimens may be effective in treating newly diagnosed chronic graft-versus-host disease caused by stem cell transplantation. It is not yet known whether immunosuppressive treatment regimens are more effective with or without mycophenolate mofetil in treating chronic graft-versus-host disease.
PURPOSE: This randomized phase III trial is studying whether the addition of mycophenolate mofetil improves the efficacy of immunosuppressive treatment regimens in patients with newly diagnosed chronic graft-versus-host disease.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized Study to Evaluate The Efficacy of Mycophenolate Mofetil Added to The Systemic Immunosuppressive Regimen First Used For Treatment of Chronic Graft-Versus-Host Disease|
- Cure of Chronic GVHD Without Resorting to Secondary Systemic Therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]Withdrawal of all systemic immunosuppressive treatment after resolution of chronic GVHD, before death or onset of recurrent malignancy
- Definitive Absence of Efficacy Success [ Time Frame: 2 years ] [ Designated as safety issue: No ]Administration of secondary systemic therapy for chronic GVHD, death during primary therapy, or onset of recurrent malignancy or bronchiolitis obliterans during primary therapy
- Open Label Systemic Treatment Because of Inadequate Response to Primary Therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]Administration of any systemic therapy other than the immunosuppressive agents used for initial treatment, because of persistent or progressive chronic graft-versus-host disease
- Bronchiolitis Obliterans [ Time Frame: within 4 years ] [ Designated as safety issue: No ]Development of bronchiolitis obliterans during treatment
- Recurrent Malignancy [ Time Frame: within 4 years ] [ Designated as safety issue: Yes ]Development of recurrent malignancy after enrollment in the study
- Non-relapse Mortality [ Time Frame: within 4 years ] [ Designated as safety issue: Yes ]Death without prior development of recurrent malignancy
- Death or Recurrent Malignancy [ Time Frame: within 4 years ] [ Designated as safety issue: Yes ]Death due to any cause or development of recurrent malignancy at any time after enrollment
- Death [ Time Frame: within 4 years ] [ Designated as safety issue: Yes ]Death from any cause after enrollment in the study
- Withdrawal of Prednisone [ Time Frame: within 4 years ] [ Designated as safety issue: No ]Withdrawal of treatment with prednisone after improvement or resolution of chronic GVHD
- End of Systemic Treatment [ Time Frame: within 4 years ] [ Designated as safety issue: No ]Withdrawal of all immunosuppressive treatment without recurrent malignancy
|Study Start Date:||May 2004|
|Study Completion Date:||September 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Active Comparator: Mycophenolate mofetil
Patients receive oral mycophenolate mofetil twice daily.
Drug: mycophenolate mofetil
Other Name: CellCept
Placebo Comparator: Placebo
Patients receive oral placebo twice daily
Other Name: Control
- Compare the efficacy of immunosuppressive treatment regimens with vs without mycophenolate mofetil in patients with newly diagnosed chronic graft-vs-host disease.
- Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, prospective, multicenter study. Patients are stratified according to organ involvement of chronic graft-versus-host disease (GVHD) (single organ vs multiple organs) and transplant center. Patients are randomized to 1 of 2 treatment arms.
All patients receive usual therapy for chronic GVHD comprising oral prednisone twice daily and oral cyclosporine, oral tacrolimus or oral sirolimus twice daily until 2 weeks after the first evidence of improvement of symptoms of chronic GVHD.
- Arm I: Patients receive oral mycophenolate mofetil twice daily.
- Arm II: Patients receive oral placebo twice daily. In both arms administration of the study drug continues for 3 months after completion of prednisone and cyclosporine, tacrolimus or sirolimus in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and then every 3 months.
Patients are followed every 3 months for 3-5 years.
PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within 3 years.
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|Stanford Cancer Center|
|Stanford, California, United States, 94305-5824|
|United States, Florida|
|University of Florida Shands Cancer Center|
|Gainesville, Florida, United States, 32610-100277|
|United States, Illinois|
|University of Chicago Cancer Research Center|
|Chicago, Illinois, United States, 60637-1470|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109-0942|
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Nebraska|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198-3330|
|United States, New Jersey|
|Hackensack University Medical Center Cancer Center|
|Hackensack, New Jersey, United States, 07601|
|United States, Oregon|
|Oregon Health and Science University Cancer Institute|
|Portland, Oregon, United States, 97239-3098|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|United States, Texas|
|Baylor University Medical Center - Dallas|
|Dallas, Texas, United States, 75246|
|M. D. Anderson Cancer Center at University of Texas|
|Houston, Texas, United States, 77030-4009|
|Texas Transplant Institute|
|San Antonio, Texas, United States, 78229|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|University of Washington School of Medicine|
|Seattle, Washington, United States, 98195|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Paul J. Martin, MD||Fred Hutchinson Cancer Research Center|