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
Lc. Platanias et al., 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, Leukemia & lymphoma, 14(3-4), 1994, pp. 257-262
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.