Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma
| Autor: | John M. Kirkwood, H. Jones, E. A. Saria, R. Schwartz, Marc S. Ernstoff, D. R. Vlock, N. Wedel, K. Selvaggi, S. Ackerman |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Immunology Peripheral edema Ricin Gastroenterology Mice Internal medicine medicine Immunology and Allergy Animals Humans Hypoalbuminemia Lymph node Melanoma Aged Pharmacology medicine.diagnostic_test business.industry Immunotoxins Antibodies Monoclonal Middle Aged medicine.disease Combined Modality Therapy Immunoconjugate medicine.anatomical_structure Toxicity Antibody Formation Cyclosporine Female Lymph medicine.symptom business Liver function tests |
| Zdroj: | Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy. 13(3) |
| ISSN: | 1067-5582 |
| Popis: | XOMAZYME-Mel (XMMME-001-RTA) is an immunoconjugate comprised of ricin A chain conjugated to a murine monoclonal antibody directed against high molecular weight melanoma antigens. Although not necessarily related to increased toxicity or decreased efficacy, the development of anti-immunoconjugate antibodies may limit repetitive dosing with an immunoconjugate. We evaluated the role of cyclosporine A in blocking the antibody response in patients with melanoma treated with XMMME-001-RTA. Patients received cyclosporine in divided daily doses to achieve serum levels by HPLC of 150-200 ng/ml on days 1-22. On day 3, XMMME-001-RTA was begun at dosages 0.2-0.6 mg/kg daily for 5 days. Treatment was repeated every 35 days. Three patients were treated in each dosage tier (0.2, 0.4, 0.6 mg/kg). Nine patients were entered and all nine were evaluable. Patients had histologically confirmed melanoma. Metastatic sites included skin, soft tissue, and lymph nodes (seven), lung (two), liver (one), and spleen (one). There were four men and five women aged 46-75 years. Toxicities included myalgia, arthralgia, hypoalbuminemia, fatigue, elevations in liver function tests, and increased peripheral edema. Four patients received two to five repeated dosages of XMMME-001-RTA. One wheal-and-flare reaction from an immunotoxin test dose of XMMME-001-RTA was noted after five cycles. After a test dose subsequent to one cycle, two patients experienced chest tightness without ECG changes and were removed from the study. All toxicities resolved without sequelae. One patient experienced partial lymph node remission for 9 months. A second patient had stable mediastinal disease for 20 months. XMMME-001-RTA is safe when given repeatedly with cyclosporine. |
| Databáze: | OpenAIRE |
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