A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia
Details
Publication Year 2015-05, Volume 56, Issue #5, Page 1406-1415
Journal Title
Leuk Lymphoma
Publication Type
Journal Article
Abstract
Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-alpha (CD123). CSL360 is a recombinant, chimeric immunoglobulin G1 (IgG1), anti-CD123 monoclonal antibody (MoAb) that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. This phase 1 study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels (0.1-10.0 mg/kg). Other than mild infusion reactions, CSL360 was well tolerated. The maximal tolerated dose was not reached. The half-life was 4.9 days, and the area under the curve (AUC) and maximum concentration (Cmax) increased proportionally with dose. Doses >/= 3.0 mg/kg resulted in complete saturation and down-regulation of CD123 and abolition of ex vivo proliferative responsiveness to IL-3, indicating adequate blockade of IL-3 signaling. Two patients responded, with one remaining in complete remission after 17 doses. CSL360 bound CD123 specifically, but did not induce anti-leukemic activity in most patients. While safe, MoAb blockade of CD123 function is insufficient as a therapeutic strategy.
Publisher
Informa
WEHI Research Division(s)
Cancer And Haematology
PubMed ID
25248882
NHMRC Grants
NHMRC/461219 NHMRC/637309 NHMRC/1016647
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-05-19 02:05:28
Last Modified: 2016-01-13 02:20:04
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