TY - JOUR
T1 - Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies
AU - Platanias, Leonidas C.
AU - Ratain, Mark J.
AU - O'brien, Sheila
AU - Larson, Richard A.
AU - Vardiman, James W.
AU - Shaw, Jill P.
AU - Williams, Stephanie F.
AU - Baron, Joseph M.
AU - Parker, Karen
AU - Woodworth, Thasia G.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - DAB486IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene with the sequences for human interleukin-2 (IL-2). It selectively binds to and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were entered in a phase I study of DAB486IL-2, administered as a 6 hour continuous 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 doses. The starting dose was 0.1 mg/kg/day with increments of 0.1 mg/kg/day per dose level up to 0.3 mg/kg/day. Significant adverse effects included transient asymptomatic elevation of liver transaminases, hypersensitivity, 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, previously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient highly refractory to chemotherapy suggests that DAB486IL-2 may have efficacy in selected patients whose malignant cells express the IL-2 receptor.
AB - DAB486IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene with the sequences for human interleukin-2 (IL-2). It selectively binds to and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were entered in a phase I study of DAB486IL-2, administered as a 6 hour continuous 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 doses. The starting dose was 0.1 mg/kg/day with increments of 0.1 mg/kg/day per dose level up to 0.3 mg/kg/day. Significant adverse effects included transient asymptomatic elevation of liver transaminases, hypersensitivity, 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, previously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient highly refractory to chemotherapy suggests that DAB486IL-2 may have efficacy in selected patients whose malignant cells express the IL-2 receptor.
KW - Hematologic neoplasms
KW - IL-2 fusion toxin
KW - Phase I trial
UR - http://www.scopus.com/inward/record.url?scp=0028058794&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028058794&partnerID=8YFLogxK
U2 - 10.3109/10428199409049676
DO - 10.3109/10428199409049676
M3 - Article
C2 - 7950914
AN - SCOPUS:0028058794
VL - 14
SP - 257
EP - 262
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 3-4
ER -