Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies

Leonidas C. Platanias*, Mark J. Ratain, Sheila O'brien, Richard A. Larson, James W. Vardiman, Jill P. Shaw, Stephanie F. Williams, Joseph M. Baron, Karen Parker, Thasia G. Woodworth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)257-262
Number of pages6
JournalLeukemia and Lymphoma
Volume14
Issue number3-4
DOIs
StatePublished - Jan 1 1994

Keywords

  • Hematologic neoplasms
  • IL-2 fusion toxin
  • Phase I trial

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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