A Pilot Study Evaluating the CD34+ Cell Mobilizing Activity and Adverse Events Associated with Escalating Doses of AMD3100 in Healthy Volunteers.
Authors: Lemery Steven J. , Hsieh Matthew M. , Smith Aleah , Rao Sheila , Khuu Hanh M. , Theresa Donohue , Karpovich Jennifer M. , Cook Lisa , Goodwin Rose , Boss Carol , Calandra Gary , Geller Nancy , Tisdale John , Childs Richard 
Published: October 2019

Abstract
Background: AMD3100 (AMD or plerixafor) inhibits the binding of SDF-1 to its cognate receptor CXCR4 resulting in the rapid mobilization of CD34+ hematopoietic progenitor cells into the peripheral circulation. A prior phase I study suggested peak CD34+ cell mobilization occurred 6–8 hours following a 240 mcg/kg dose of AMD. This investigation provides preliminary data on the safety and CD34+ cell mobilizing effects of doses up to 480 mcg/kg of AMD.
Methods: To account for inter-subject variability, subjects in three cohorts received two different subcutaneous doses of AMD. Healthy volunteers received the following doses of AMD: 240 mcg/kg and 320 mcg/kg (cohort 1); 320 mcg/kg and 400 mcg/kg (cohort 2); and 400 mcg/kg and 480 mcg/kg (cohort 3). Subjects received the higher dose at least 14 days after the first to allow adequate wash-out of AMD. The absolute number of circulating CD34+ cells were measured after each dose at the following times: 0, 2, 4, 6, 8, 10, 12, 14, 18, and 24 hours. In addition, this study assessed the following parameters: adverse events, AMD pharmacokinetics (400 and 480 mcg/kg doses), cytokine polarization status (Th1 vs Th2) of AMD mobilized CD3+ T-cells, and endothelial progenitor cell measurements.
Results: To date, 16 of the planned 18 subjects have been enrolled on study with final results available for the first two cohorts; preliminary results exist for four subjects in the third cohort (400 mcg/kg vs 480 mcg/kg dose). Common toxicities include diarrhea, nausea, sinus tachycardia, injection site redness, perioral paresthesias, and headache. No dose limiting toxicities were observed; however, the frequency and/or magnitude of headache, nausea, vomiting, diarrhea, and tachycardia were greater at the 400 mcg/kg dose. Table 1 summarizes the preliminary CD34+ mobilization results for the 240, 320, and 400 mcg/kg doses. The lines in figures 1 and 2 show the difference in an individual subjects peak CD34+ cell number mobilized following 2 different doses of AMD.
Conclusion: Although this phase I study is ongoing, preliminary data suggest doses of AMD higher than 240 mcg/kg may improve the peak numbers of CD34+ cells mobilized into the circulation. Furthermore, although dose escalation continues, the adverse events observed after a 400 mcg/kg dose of AMD appear similar to those observed after lower doses; no grade 3 or 4 adverse events have been observed. The final study results will provide additional data on the dose of AMD that optimizes CD34+ cell and CFU-GM mobilization for both autologous and allogeneic hematopoietic stem cell collections.
CD 34+ cell mobilization 240 mcg/kg 320 mcg/kg 400 mcg/kg *Two subjects in 400 mcg dose group had the same peak mobilization time at two time points: these were averaged Number of subjects 6 12 10 Mean mobilized CD34 cells/microliter 27 29 31 Standard deviation of CD34 cells/microliter 13 14 13 Average peak mobilization time in hours* 9 10 11 Range of peak mobilization times in hours 8−14 6−14 8−18 Figure Figure