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.
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Authors | Arthur Frankel, Jen-Sing Liu, David Rizzieri, Donna Hogge |
Journal | Leukemia & lymphoma
(Leuk Lymphoma)
Vol. 49
Issue 3
Pg. 543-53
(Mar 2008)
ISSN: 1029-2403 [Electronic] United States |
PMID | 18297533
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Diphtheria Toxin
- Interleukin-3
- Isoantibodies
- Recombinant Fusion Proteins
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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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