1. Academic Validation
  2. Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers-results of a dose escalation trial

Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers-results of a dose escalation trial

  • J Transl Med. 2017 Jan 3;15(1):2. doi: 10.1186/s12967-016-1107-2.
Darja Karpova 1 2 Susanne Bräuninger 1 Eliza Wiercinska 1 Ariane Krämer 1 Belinda Stock 1 Jochen Graff 3 Hans Martin 4 Achim Wach 5 Christophe Escot 5 Garry Douglas 5 Barbara Romagnoli 5 Eric Chevalier 5 Klaus Dembowski 5 Leon Hooftman 5 Halvard Bonig 6 7 8
Affiliations

Affiliations

  • 1 German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.
  • 2 Department of Internal Medicine, Division of Oncology, Section of Stem Cell Biology, Washington University Medical School, St. Louis, MO, USA.
  • 3 Clinical Trial Center Rhein-Main (KSRM), Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt, Germany.
  • 4 Department of Medicine II, Goethe University, Frankfurt, Germany.
  • 5 Polyphor Ltd, Allschwil, Switzerland.
  • 6 German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany. hbonig@uw.edu.
  • 7 Institute for Transfusion Medicine and Immunohematology, Goethe University, Sandhofstr. 1, 60528, Frankfurt, Germany. hbonig@uw.edu.
  • 8 Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA. hbonig@uw.edu.
Abstract

Background: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 Antagonist POL6326 (balixafortide) vs. G-CSF.

Methods: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1-2 h infusion of 500-2500 µg/kg of balixafortide. Safety, tolerability, pharmacokinetics and pharmacodynamics were assessed.

Results: Balixafortide was well tolerated and rated favorably over G-CSF by subjects. At all doses tested balixafortide mobilized HSPC. In the dose range between 1500 and 2500 µg/kg mobilization was similar, reaching 38.2 ± 2.8 CD34 + cells/µL (mean ± SEM). Balixafortide caused mixed leukocytosis in the mid-20 K/µL range. B-lymphocytosis was more pronounced, whereas neutrophilia and monocytosis were markedly less accentuated with balixafortide compared to G-CSF. At the 24 h time point, leukocytes had largely normalized.

Conclusions: Balixafortide is safe, well tolerated, and induces efficient mobilization of HSPCs in healthy male volunteers. Based on experience with current apheresis technology, the observed mobilization at doses ≥1500 µg/kg of balixafortide is predicted to yield in a single apheresis a standard dose of 4× 10E6 CD34+ cells/kg from most individuals donating for an approximately weight-matched recipient. Exploration of alternative dosing regimens may provide even higher mobilization responses. Trial Registration European Medicines Agency (EudraCT-Nr. 2011-003316-23) and clinicaltrials.gov (NCT01841476).

Keywords

Apheresis; CXCR4; Clinical trial; G-CSF; Mobilization; PEM-technology; Plasmacytoid dendritic cell; Plerixafor; Stem cell; Transplantation.

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