Phase I/II Study of Murine Monoclonal Antibody-Ricin A Chain (XOMAZYME-Mel) Immunoconjugate plus Cyclosporine A in Patients with Metastatic Melanoma

Kathy Selvaggi, E. A. Saria, R. Schwartz, D. R. Vlock, S. Ackerman, N. Wedel, J. M. Kirkwood, H. Jones, M. S. Ernstoff

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalJournal of Immunotherapy
Volume13
Issue number3
DOIs
StatePublished - Jan 1 1993

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Immunoconjugates
Ricin
Cyclosporine
Melanoma
Monoclonal Antibodies
Lymph Nodes
Mediastinal Diseases
Melanoma-Specific Antigens
Immunotoxins
Hypoalbuminemia
Blocking Antibodies
Liver Function Tests
Myalgia
Arthralgia
Antibody Formation
Fatigue
Anti-Idiotypic Antibodies
Edema
Electrocardiography
Thorax

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Selvaggi, Kathy ; Saria, E. A. ; Schwartz, R. ; Vlock, D. R. ; Ackerman, S. ; Wedel, N. ; Kirkwood, J. M. ; Jones, H. ; Ernstoff, M. S. / Phase I/II Study of Murine Monoclonal Antibody-Ricin A Chain (XOMAZYME-Mel) Immunoconjugate plus Cyclosporine A in Patients with Metastatic Melanoma. In: Journal of Immunotherapy. 1993 ; Vol. 13, No. 3. pp. 201-207.
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Phase I/II Study of Murine Monoclonal Antibody-Ricin A Chain (XOMAZYME-Mel) Immunoconjugate plus Cyclosporine A in Patients with Metastatic Melanoma. / Selvaggi, Kathy; Saria, E. A.; Schwartz, R.; Vlock, D. R.; Ackerman, S.; Wedel, N.; Kirkwood, J. M.; Jones, H.; Ernstoff, M. S.

In: Journal of Immunotherapy, Vol. 13, No. 3, 01.01.1993, p. 201-207.

Research output: Contribution to journalArticle

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T1 - Phase I/II Study of Murine Monoclonal Antibody-Ricin A Chain (XOMAZYME-Mel) Immunoconjugate plus Cyclosporine A in Patients with Metastatic Melanoma

AU - Selvaggi, Kathy

AU - Saria, E. A.

AU - Schwartz, R.

AU - Vlock, D. R.

AU - Ackerman, S.

AU - Wedel, N.

AU - Kirkwood, J. M.

AU - Jones, H.

AU - Ernstoff, M. S.

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N2 - 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.

AB - 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.

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