Journal article
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
SZ He, S Busfield, DS Ritchie, MS Hertzberg, S Durrant, ID Lewis, P Marlton, AJ McLachlan, I Kerridge, KF Bradstock, G Kennedy, AW Boyd, TM Yeadon, AF Lopez, HS Ramshaw, H Iland, S Bamford, M Barnden, M Dewitte, R Basser Show all
Leukemia and Lymphoma | Published : 2015
Abstract
Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-α (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 ..
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Awarded by Victorian Cancer Agency
Funding Acknowledgements
This trial was funded by CSL Ltd.We thank all patients participating in the study, and the research nurses who worked with us during its conduct. We also thank Dr. David Gearing for his role in the preclinical development of CSL360, and for helpful discussions. We would like to thank Mark Biondo, Sarah Hosback and Rosyln Davis from CSL Ltd. for developing, validating and performing the pharmacodynamics and PK and immunogenicity assays. S.Z.H. was supported by a Webster scholarship (Melbourne Health) and Max Whiteside Clinical Fellowship (Leukaemia Foundation of Australia); A.W.R.'s work was supported by a fellowship from the Victorian Cancer Agency and grants (461219, 637309, 1016647) from the National Health and Medical Research Council (NHMRC) of Australia; A.F.L.'s work was supported by grants from the NHMRC and from Cancer Australia; H.S.R.'s work was supported by the Peter Nelson Leukaemia Research Fund.