Title |
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
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Published in |
Leukemia & Lymphoma, November 2014
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DOI | 10.3109/10428194.2014.956316 |
Pubmed ID | |
Authors |
Simon Z. He, Samantha Busfield, David S. Ritchie, Mark S. Hertzberg, Simon Durrant, Ian D. Lewis, Paula Marlton, Andrew J. McLachlan, Ian Kerridge, Kenneth F. Bradstock, Glen Kennedy, Andrew W. Boyd, Trina M. Yeadon, Angel F. Lopez, Hayley S. Ramshaw, Harry Iland, Simone Bamford, Megan Barnden, Mark DeWitte, Russell Basser, Andrew W. Roberts |
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 ≥ 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. |
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Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
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United States | 2 | 2% |
Unknown | 99 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 15 | 15% |
Student > Ph. D. Student | 12 | 12% |
Student > Master | 11 | 11% |
Student > Bachelor | 11 | 11% |
Student > Postgraduate | 6 | 6% |
Other | 17 | 17% |
Unknown | 29 | 29% |
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Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
Other | 3 | 3% |
Unknown | 32 | 32% |