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Phase I trial of an interleukin‐2 fusion toxin (DAB486IL‐2) in hematologic malignancies: Complete response in a patient with Hodgkin's disease refractory to chemotherapy
Author(s) -
Tepler Isidore,
Schwartz Gary,
Parker Karen,
Charette Jane,
Kadin Marshall E.,
Woodworth Thasia G.,
Schnipper Lowell E.
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940215)73:4<1276::aid-cncr2820730424>3.0.co;2-d
Subject(s) - medicine , diphtheria toxin , adverse effect , gastroenterology , lymphoma , immunology , tolerability , toxin , biochemistry , chemistry
Background . DAB 486 IL‐2 is a recombinant fusion toxin in which the native diphtheria toxin‐receptor binding‐domain has been replaced with human interleukin‐2 (IL‐2). This molecule is specifically cytotoxic in vitro within 30 minutes for cells that express the high‐affinity IL‐2 receptor (IL‐2R). Methods . This was a Phase I/II study of DAB 486 IL‐2 as a brief infusion in 15 patients with refractory lymphoid malignancies. Five patients per cohort received DAB 486 IL‐2 as a 30–60 minute intravenous infusion at dose levels of 0.075, 0.115, and 0.2 mg/kg daily for 5 days. Results . The maximal tolerated dose (MTD) of DAB 486 IL‐2 was determined to be 0.2 mg/kg daily on the basis of hypersensitivity‐like symptoms and reversible hepatic transaminase elevations. Other adverse effects included mild creatinine elevations, proteinuria, and hypoalbuminemia. The presence of antibodies to diphtheria toxin or DAB 486 IL‐2 was correlated with hypersensitivity‐like effects but did not prevent an antitumor effect. One complete response was observed in a patient with Hodgkin's disease in relapse with bilateral pulmonary nodules after autologous bone marrow transplantation. He remains free of disease more than 2 years after completion of therapy. Conclusions . The dramatic antitumor response seen in one patient and the relative tolerability of DAB 486 IL‐2 indicates the potential utility of this targeted agent in IL‐2‐expressing hematologic malignancies. Cancer 1994; 73:1276–85.