title: A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease.
abstract: Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. macmi002@umn.edu
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Macmillan
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Gisela
authors.initials: G
authors.lastname: Schwab
authors.forename: Nancy
authors.initials: N
authors.lastname: Havrilla
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.forename: Saling
authors.initials: S
authors.lastname: Huang
authors.forename: Lorin
authors.initials: L
authors.lastname: Roskos
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.forename: Richard K
authors.initials: RK
authors.lastname: Shadduck
authors.forename: John
authors.initials: J
authors.lastname: Dipersio
authors.forename: Mary
authors.initials: M
authors.lastname: Territo
authors.forename: Steve
authors.initials: S
authors.lastname: Pavletic
authors.forename: Charles
authors.initials: C
authors.lastname: Linker
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D051926:Basigin / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D013256:Steroids / Q000494:pharmacology*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; C497886:BSG protein, human; D013256:Steroids; D051926:Basigin