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 language | English (US) |
---|---|
Pages (from-to) | 543-553 |
Number of pages | 11 |
Journal | Leukemia and Lymphoma |
Volume | 49 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2008 |
Keywords
- Acute myeloid leukemia
- Diphtheria toxin
- Interleukin-3
- Myelodysplasia
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research