PHASE-I TRIAL OF A GENETICALLY-ENGINEERED INTERLEUKIN-2 FUSION TOXIN (DAB(486)IL-2) AS A 6-HOUR INTRAVENOUS-INFUSION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

DAB(486)IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene wit h the sequences for human interleukin-2 (IL-2). It selectively binds t o and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were ent ered in a phase I study of DAB(486)IL-2, administered as a 6 hour cont inuous intravenous infusion on days 1, 2, 8, 9, 15, and 16 of each 28 day cycle. Cohorts of 3 to 6 patients were treated with escalating dos es. The starting dose was 0. 1 mg/kg/day with increments of O.1 mg/kg/ day per dose level up to 0.3 mg/kg/day. Significant adverse effects in cluded transient asymptomatic elevation of liver transaminases, hypers ensitivity, anemia, thrombocytopenia, fever, and creatinine elevation. A partial response of approximately nine months duration was observed in a patient with small cell lymphocytic non-Hodgkin's lymphoma, prev iously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient hi ghly refractory to chemotherapy suggests that DAB(486)IL-2 may have ef ficacy in selected patients whose malignant cells express the IL-2 rec eptor.