title: Phase Ia-Ib trial of an anti-GD3 monoclonal antibody in combination with interferon-alpha in patients with malignant melanoma.
abstract: A phase Ia-Ib study was undertaken to treat melanoma patients with a constant dose of the anti-GD3 monoclonal antibody, R24, in combination with increasing dose levels of recombinant interferon-alpha (rHuIFN alpha-2a). Fifteen patients were treated on days 1-5 and 8-12 with a continuous 6-h i.v. infusion of R24 (8 mg/m2) and escalating i.m. doses of rHuIFN alpha-2a. Peripheral blood lymphocytes were obtained at multiple times before and during treatment and monitored for changes in lymphocyte subpopulations and changes in natural killer and antibody-dependent cellular toxicity functional activity. There were no consistent changes in most immune parameters; however, there was a decrease from pretreatment levels in the suppressor T cell (CD8+, CD11b+) subset and a dose-dependent decrease in the helper/inducer (CD4+, Leu-8+) T cell subset. The peak serum concentration of R24 was reached on day 5 of the study and was 9.4 micrograms/ml. During the second week of treatment, peak serum levels of R24 fell to less than 4 micrograms/ml. This finding was related to the development of human antimouse antibody, which would be detected as early as day 8 of the study. Binding of mouse Ig (R24) within the tumor bed was observed in 5 of 12 biopsy specimens. The maximal tolerated dose of the combination was dose level IV, in which patients received 8 mg/m2 of R24 and 50 x 10(6) units of rHuIFN alpha-2a on days 1-5 and 8-12 of treatment.
authors.affiliation: Section of Immunology, Cleveland Clinic Foundation, Ohio 44195.
authors.forename: M J
authors.initials: MJ
authors.lastname: Caulfield
authors.forename: B
authors.initials: B
authors.lastname: Barna
authors.forename: S
authors.initials: S
authors.lastname: Murthy
authors.forename: R
authors.initials: R
authors.lastname: Tubbs
authors.forename: J
authors.initials: J
authors.lastname: Sergi
authors.forename: S
authors.initials: S
authors.lastname: Medendorp
authors.forename: R M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D000911:Antibodies, Monoclonal; D005732:Gangliosides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C026226:ganglioside, GD3