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

Leuk Lymphoma. 2015 May;56(5):1406-15. doi: 10.3109/10428194.2014.956316. Epub 2014 Nov 20.


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.

Keywords: Acute myeloid leukemia (AML); immunotherapy; interleukin-3 (IL-3) receptor-α (CD123); leukemic stem cell (LSC).

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Interleukin-3 / metabolism
  • Interleukin-3 Receptor alpha Subunit / antagonists & inhibitors
  • Interleukin-3 Receptor alpha Subunit / genetics
  • Interleukin-3 Receptor alpha Subunit / metabolism
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • Recurrence
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CSL360
  • Interleukin-3
  • Interleukin-3 Receptor alpha Subunit