Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia

Arthur Frankel, Jen Sing Liu, David Rizzieri, Donna Hogge

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

DT388IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose was & 12.5 μg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT388IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT388IL3 antibodies developed in most patients between day 15 and 30. Of 40 evaluable AML patients, 1 had a CR (8 months) and 1 had PR (3 months). Of 5 MDS patients, 1 had a PR (4 months). Because of the prolonged infusion schedule, many patients failed to receive six doses. DT388IL3 produces remissions in patients with relapsed/ refractory AML and MDS with minimal toxicities, and alternate schedules of administration are needed to enhance the response rate.

Original languageEnglish (US)
Pages (from-to)543-553
Number of pages11
JournalLeukemia and Lymphoma
Volume49
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Acute myeloid leukemia
  • Diphtheria toxin
  • Interleukin-3
  • Myelodysplasia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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