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


Journal Article

DT(388)IL3 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 microg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT(388)IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT(388)IL3 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. DT(388)IL3 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.

Full Text

Duke Authors

Cited Authors

  • Frankel, A; Liu, J-S; Rizzieri, D; Hogge, D

Published Date

  • March 2008

Published In

Volume / Issue

  • 49 / 3

Start / End Page

  • 543 - 553

PubMed ID

  • 18297533

Pubmed Central ID

  • 18297533

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

Digital Object Identifier (DOI)

  • 10.1080/10428190701799035


  • eng

Conference Location

  • United States