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

Abstract
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.
AuthorsArthur Frankel, Jen-Sing Liu, David Rizzieri, Donna Hogge
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 49 Issue 3 Pg. 543-53 (Mar 2008) ISSN: 1029-2403 [Electronic] United States
PMID18297533 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Diphtheria Toxin
  • Interleukin-3
  • Isoantibodies
  • Recombinant Fusion Proteins
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Diphtheria Toxin (administration & dosage, therapeutic use)
  • Female
  • Humans
  • Interleukin-3 (administration & dosage, therapeutic use)
  • Isoantibodies (biosynthesis, blood)
  • Leukemia, Myeloid, Acute (complications, drug therapy)
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Myelodysplastic Syndromes (complications, drug therapy)
  • Recombinant Fusion Proteins (immunology, therapeutic use, toxicity)
  • Remission Induction (methods)
  • Salvage Therapy (methods)
  • Treatment Outcome

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