Phase I Trial of a 90-Minute Infusion of the Fusion Toxin DAB486IL-2 in Hematological Cancers

C. F. LeMaistre, Fiona E. Craig, Carole Meneghetti, Becky McMullin, David H. Boldt, James Reuben, Michael Rosenblum, Karen Parker, Thasia Woodworth

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

DAB486IL-2, a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemotherapy refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we conducted a single arm, dose escalation study of a 90-min infusion of DAB^IL^ daily for 5 days. Patients with cancers of a histology previously reported to express the p55 component of the IL-2 receptor and who could not receive potentially more effective therapy were eligible for enrollment. Fifteen men and 8 women with a median age of 49 years were given a total of 51 courses of DAB486IL-2. The maximum tolerated dose was 0.3 mg/kg/day defined by renal insufficiency associated with hemolysis and thrombocytopenia. The clearance of DAB^IL^ from serum fit a one-compartment model with a half-life of 11.5 - 4.3 (SD) min at the 0.2-mg/kg dose. Two patients sustained a partial response and 4 patients had tumor reduction not qualifying for an objective response. No tumors that were negative for expression of the p55 subunit of the receptor responded to DAB486IL-2 treatment. Reduction in size occurred in 2 tumors in which p55 expression was unknown and 4 patients with tumors that were known to be p55 positive. Dosing determined by specific activity rather than mass also appeared to be an important determinant of response. This study suggests that the presence of p55 expression on tumor cells is necessary, but alone may not be sufficient to achieve a tumor response. The correlation of additional variables such as specific activity of DAB486IL-2 and tumor expression of the p75 subunit of the IL-2 receptor and receptor function will also require further study.

Original languageEnglish (US)
Pages (from-to)3930-3934
Number of pages5
JournalCancer Research
Volume53
Issue number17
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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