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
- Author(s)
- He, SZ; Busfield, S; Ritchie, DS; Hertzberg, MS; Durrant, S; Lewis, ID; Marlton, P; McLachlan, AJ; Kerridge, I; Bradstock, KF; Kennedy, G; Boyd, AW; Yeadon, TM; Lopez, AF; Ramshaw, HS; Iland, H; Bamford, S; Barnden, M; DeWitte, M; Basser, R; Roberts, AW;
- 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
- Research Division(s)
- Cancer And Haematology
- PubMed ID
- 25248882
- Publisher's Version
- https://doi.org/10.3109/10428194.2014.956316
- NHMRC Grants
- NHMRC/461219, NHMRC/637309, NHMRC/1016647,
- Terms of Use/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