title: Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802.
abstract: Corticosteroids are the accepted primary therapy for acute graft-versus-host disease (GVHD), but durable responses are seen in only about half of the patients. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0802, a phase 3 multicenter randomized double-blinded trial, was designed to test whether mycophenolate mofetil (MMF) plus corticosteroids was superior to corticosteroids alone as initial therapy for acute GVHD. Patients with newly diagnosed acute GVHD were eligible if they required systemic therapy. Patients were randomized to receive prednisone with either MMF or placebo. The primary end point was acute or chronic GVHD-free survival at day 56 after initiation of therapy. A futility rule for GVHD-free survival at day 56 was met at a planned interim analysis after 235 patients (of 372) were enrolled: 116 MMF, 119 placebo. Baseline characteristics were well balanced between treatment groups including grade and organ distribution of GVHD. GVHD-free survival at day 56, cumulative incidence of chronic GVHD at 12 months, overall survival, Epstein-Barr virus reactivation, severe, life-threatening infections, relapse at 12 months, and quality of life were similar. The addition of MMF to corticosteroids as initial therapy for acute GVHD does not improve GVHD-free survival compared with corticosteroids alone. This trial was registered at www.clinicaltrials.gov as #NCT01002742.
authors.affiliation: Bone Marrow Transplant Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD;
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Brent R
authors.initials: BR
authors.lastname: Logan
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapies, MD Anderson Cancer Center, Houston, TX;
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.affiliation: Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA;
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: The Emmes Corporation, Rockville, MD;
authors.forename: Kate
authors.initials: K
authors.lastname: Barowski
authors.affiliation: The Emmes Corporation, Rockville, MD;
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Carter
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI;
authors.forename: Steven C
authors.initials: SC
authors.lastname: Goldstein
authors.affiliation: Department of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA;
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Hexner
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI;
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN;
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: The Emmes Corporation, Rockville, MD;
authors.forename: Adam M
authors.initials: AM
authors.lastname: Mendizabal
authors.affiliation: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA;
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Pasquini
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, MN; and.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Peter
authors.initials: P
authors.lastname: Westervelt
authors.affiliation: Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA;
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010919:Placebos; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000379:methods; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D010919:Placebos; D009173:Mycophenolic Acid; D011241:Prednisone