Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease.
We conducted a double-blind, randomized multicenter trial to determine whether the addition of mycophenolate mofetil (MMF) improves the efficacy of initial systemic treatment of chronic graft-versus-host disease (GVHD). The primary endpoint was resolution of chronic GVHD and withdrawal of all systemic treatment within 2 years, without secondary treatment. Enrollment of 230 patients was planned, providing 90% power to observe a 20% difference in success rates between the 2 arms. The study was closed after 4 years because the interim estimated cumulative incidence of success for the primary endpoint was 23% among 74 patients in the MMF arm and 18% among 77 patients in the control arm, indicating a low probability of positive results for the primary endpoint after completing the study as originally planned. Analysis of secondary endpoints showed no evidence of benefit from adding MMF to the systemic regimen first used for treatment of chronic GVHD. The estimated hazard ratio of death was 1.99 (95% confidence interval, 0.9-4.3) among patients in the MMF arm compared with the control arm. MMF should not be added to the initial systemic treatment regimen for chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00089141 on August 4, 2004.
Martin
Paul J
PJ
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. pmartin@fhcrc.org
Storer
Barry E
BE
Rowley
Scott D
SD
Flowers
Mary E D
ME
Lee
Stephanie J
SJ
Carpenter
Paul A
PA
Wingard
John R
JR
Shaughnessy
Paul J
PJ
DeVetten
Marcel P
MP
Jagasia
Madan
M
Fay
Joseph W
JW
van Besien
Koen
K
Gupta
Vikas
V
Kitko
Carrie
C
Johnston
Laura J
LJ
Maziarz
Richard T
RT
Arora
Mukta
M
Jacobson
Pamala A
PA
Weisdorf
Daniel
D
D002423:Cause of Death; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate; D016896:Treatment Outcome
D009173:Mycophenolic Acid