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

He, Simon Z., Busfield, Samantha, Ritchie, David S., Hertzberg, Mark S., Durrant, Simon, Lewis, Ian D., Marlton, Paula, McLachlan, Andrew J., Kerridge, Ian, Bradstock, Kenneth F., Kennedy, Glen, Boyd, Andrew W., Yeadon, Trina M., Lopez, Angel F., Ramshaw, Hayley S., Iland, Harry, Bamford, Simone, Barnden, Megan, DeWitte, Mark, Basser, Russell and Roberts, Andrew W. (2015) 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. Leukemia and Lymphoma, 56 5: 1406-1415. doi:10.3109/10428194.2014.956316


Author He, Simon Z.
Busfield, Samantha
Ritchie, David S.
Hertzberg, Mark S.
Durrant, Simon
Lewis, Ian D.
Marlton, Paula
McLachlan, Andrew J.
Kerridge, Ian
Bradstock, Kenneth F.
Kennedy, Glen
Boyd, Andrew W.
Yeadon, Trina M.
Lopez, Angel F.
Ramshaw, Hayley S.
Iland, Harry
Bamford, Simone
Barnden, Megan
DeWitte, Mark
Basser, Russell
Roberts, Andrew W.
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
Journal name Leukemia and Lymphoma   Check publisher's open access policy
ISSN 1029-2403
1042-8194
Publication date 2015-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.3109/10428194.2014.956316
Volume 56
Issue 5
Start page 1406
End page 1415
Total pages 10
Place of publication London, United Kingdom
Publisher Informa Healthcare
Collection year 2016
Language eng
Formatted 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.
Keyword Acute myeloid leukemia (AML)
Immunotherapy
Interleukin-3 (IL-3) receptor-α (CD123)
Leukemic stem cell (LSC)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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