A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid-refractory acute graft-versus-host disease.
Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
Carpenter
Paul A
PA
Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Ave. N., Mailstop D5-290, Seattle, WA 98109, USA. pcarpent@fhcrc.org
Lowder
James
J
Johnston
Laura
L
Frangoul
Haydar
H
Khoury
Hanna
H
Parker
Pablo
P
Jerome
Keith R
KR
McCune
Jeannine S
JS
Storer
Barry
B
Martin
Paul
P
Appelbaum
Frederick
F
Abonour
Rafat
R
Westervelt
Peter
P
Anasetti
Claudio
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D013256:Steroids / Q000008:administration & dosage; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D013256:Steroids; C456519:visilizumab