title: Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers-results of a dose escalation trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
authors.affiliation: German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.|Department of Internal Medicine, Division of Oncology, Section of Stem Cell Biology, Washington University Medical School, St. Louis, MO, USA.
authors.forename: Darja
authors.initials: D
authors.lastname: Karpova
authors.affiliation: German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bräuninger
authors.affiliation: German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.
authors.forename: Eliza
authors.initials: E
authors.lastname: Wiercinska
authors.affiliation: German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Krämer
authors.affiliation: German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.
authors.forename: Belinda
authors.initials: B
authors.lastname: Stock
authors.affiliation: Clinical Trial Center Rhein-Main (KSRM), Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Graff
authors.affiliation: Department of Medicine II, Goethe University, Frankfurt, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Martin
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Wach
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Escot
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Garry
authors.initials: G
authors.lastname: Douglas
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Romagnoli
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevalier
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dembowski
authors.affiliation: Polyphor Ltd, Allschwil, Switzerland.
authors.forename: Leon
authors.initials: L
authors.lastname: Hooftman
authors.affiliation: German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany. hbonig@uw.edu.|Institute for Transfusion Medicine and Immunohematology, Goethe University, Sandhofstr. 1, 60528, Frankfurt, Germany. hbonig@uw.edu.|Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA. hbonig@uw.edu.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D064368:Healthy Volunteers; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects; D006801:Humans; D008297:Male; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; D010455:Peptides; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4; C000624271:balixafortide; D016179:Granulocyte Colony-Stimulating Factor
keywords: Apheresis; CXCR4; Clinical trial; G-CSF; Mobilization; PEM-technology; Plasmacytoid dendritic cell; Plerixafor; Stem cell; Transplantation