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

Abstract

Background. DAB486IL‐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 DAB486IL‐2 as a brief infusion in 15 patients with refractory lymphoid malignancies. Five patients per cohort received DAB486IL‐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 DAB486IL‐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 DAB486IL‐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 DAB486IL‐2 indicates the potential utility of this targeted agent in IL‐2‐expressing hematologic malignancies. Cancer 1994; 73:1276–85. Copyright © 1994 American Cancer Society