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

Journal of Translational Medicine

Research

Jochen Graff¹  Hans Martin²  Eliza Wiercinska³  Ariane Krämer³  Susanne Bräuninger³  Belinda Stock³  Darja Karpova⁴  Halvard Bonig⁵  Barbara Romagnoli⁶  Garry Douglas⁶  Achim Wach⁶  Klaus Dembowski⁶  Christophe Escot⁶  Eric Chevalier⁶  Leon Hooftman⁶ 

[1] Clinical Trial Center Rhein-Main (KSRM), Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt, Germany;Department of Medicine II, Goethe University, Frankfurt, Germany;German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany;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;German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany;Institute for Transfusion Medicine and Immunohematology, Goethe University, Sandhofstr. 1, 60528, Frankfurt, Germany;Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA;Polyphor Ltd, Allschwil, Switzerland;

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

DOI  :  10.1186/s12967-016-1107-2

 received in 2016-10-10, accepted in 2016-12-08,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCertain 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.MethodsHealthy 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.ResultsBalixafortide 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.ConclusionsBalixafortide 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)

【 授权许可】

CC BY   
© The Author(s) 2017