TY  - JOUR
A1  - Karpova, Darja
A1  - Bräuninger, Susanne Barbara
A1  - Wiercinska, Eliza
A1  - Krämer, Ariane
A1  - Stock, Belinda
A1  - Graff, Jochen
A1  - Martin, Hans
A1  - Wach, Achim
A1  - Escot, Christophe
A1  - Douglas, Garry
A1  - Romagnoli, Barbara
A1  - Chevalier, Eric
A1  - Dembowski, Klaus
A1  - Hooftman, Leon
A1  - Bönig, Halvard-Björn
T1  - Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers-results of a dose escalation trial
T2  - Journal of translational medicine
N2  - 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)
KW  - PEM-technology
KW  - CXCR4
KW  - Mobilization
KW  - Transplantation
KW  - Apheresis
KW  - Stem cell
KW  - Plerixafor
KW  - G-CSF
KW  - Clinical trial
KW  - Plasmacytoid dendritic cell
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44996
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-449967
SN  - 1479-5876
N1  - © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 15
IS  - 1, Art. 2
SP  - 1
EP  - 12
PB  - BioMed Central
CY  - London
ER  -