Darja Karpova, Susanne Barbara Bräuninger, Eliza Wiercinska, Ariane Krämer, Belinda Stock, Jochen Graff, Hans Martin, Achim Wach, Christophe Escot, Garry Douglas, Barbara Romagnoli, Eric Chevalier, Klaus Dembowski, Leon Hooftman, Halvard-Björn Bönig
- 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)
MetadatenAuthor: | Darja KarpovaORCiDGND, Susanne Barbara BräuningerGND, Eliza WiercinskaORCiDGND, Ariane Krämer, Belinda Stock, Jochen Graff, Hans MartinORCiD, Achim Wach, Christophe Escot, Garry Douglas, Barbara Romagnoli, Eric Chevalier, Klaus Dembowski, Leon Hooftman, Halvard-Björn BönigORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-449967 |
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DOI: | https://doi.org/10.1186/s12967-016-1107-2 |
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ISSN: | 1479-5876 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28049490 |
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Parent Title (English): | Journal of translational medicine |
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Publisher: | BioMed Central |
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Place of publication: | London |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2017/11/09 |
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Date of first Publication: | 2017/01/03 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/11/09 |
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Tag: | Apheresis; CXCR4; Clinical trial; G-CSF; Mobilization; PEM-technology; Plasmacytoid dendritic cell; Plerixafor; Stem cell; Transplantation |
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Volume: | 15 |
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Issue: | 1, Art. 2 |
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Page Number: | 12 |
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First Page: | 1 |
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Last Page: | 12 |
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Note: | © 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. |
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HeBIS-PPN: | 425322629 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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