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: M J Caulfield, B Barna, S Murthy, R Tubbs, J Sergi, S Medendorp, R M Bukowski
• Journal: Journal of biological response modifiers (J Biol Response Mod) Vol. 9 Issue 3 Pg. 319-28 (Jun 1990) ISSN: 0732-6580 [Print] United States
• PMID: 2380747 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Gangliosides
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• ganglioside, GD3

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, blood)
• Antibody Formation (drug effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cytotoxicity, Immunologic
• Drug Evaluation
• Female
• Follow-Up Studies
• Gangliosides (immunology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage)
• Lymphocytes (immunology)
• Male
• Melanoma (drug therapy, immunology, secondary)
• Middle Aged
• Recombinant Proteins