Data from Single Dose of the CXCR4 Antagonist BL-8040 Induces Rapid Mobilization for the Collection of Human CD34⁺ Cells in Healthy Volunteers

<div>Abstract<p><b>Purpose:</b> The potential of the high-affinity CXCR4 antagonist BL-8040 as a monotherapy-mobilizing agent and its derived graft composition and quality were evaluated in a phase I clinical study in healthy volunteers (NCT02073019).</p><p><b>Experimental Design:</b> The first part of the study was a randomized, double-blind, placebo-controlled dose escalation phase. The second part of the study was an open-label phase, in which 8 subjects received a single injection of BL-8040 (1 mg/kg) and approximately 4 hours later underwent a standard leukapheresis procedure. The engraftment potential of the purified mobilized CD34⁺ cells was further evaluated by transplanting the cells into NSG immunodeficient mice.</p><p><b>Results:</b> BL-8040 was found safe and well tolerated at all doses tested (0.5–1 mg/kg). The main treatment-related adverse events were mild to moderate. Transient injection site and systemic reactions were mitigated by methylprednisolone, paracetamol, and promethazine pretreatment. In the first part of the study, BL-8040 triggered rapid and substantial mobilization of WBCs and CD34⁺ cells in all tested doses. Four hours postdose, the count rose to a mean of 8, 37, 31, and 35 cells/μL (placebo, 0.5, 0.75, and 1 mg/kg, respectively). FACS analysis revealed substantial mobilization of immature dendritic, T, B, and NK cells. In the second part, the mean CD34⁺ cells/kg collected were 11.6 × 10⁶ cells/kg. The graft composition was rich in immune cells.</p><p><b>Conclusions:</b> The current data demonstrate that BL-8040 is a safe and effective monotherapy strategy for the collection of large amounts of CD34⁺ cells and immune cells in a one-day procedure for allogeneic HSPC transplantation. <i>Clin Cancer Res; 23(22); 6790–801. ©2017 AACR</i>.</p></div>