Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia.
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.
Frankel
Arthur
A
Scott & White Cancer Research Institute, Temple, TX, USA.
Liu
Jen-Sing
JS
Rizzieri
David
D
Hogge
Donna
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage* / Q000627:therapeutic use; D007518:Isoantibodies / Q000096:biosynthesis / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use* / Q000633:toxicity; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome
D004167:Diphtheria Toxin; D007377:Interleukin-3; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins