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

Purpose: 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>Experimental Design: 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 (1mg/kg) and approximately 4hrs later underwent a standard leukapheresis procedure. The engraftment potential of the purified mobilized CD34+ cells was further evaluated by transplanting the cells into NSG immune deficient mice.</p> <p>Results: BL-8040 was found safe and well tolerated at all doses tested (0.5-1 mg/kg). The main treatment related AEs were mild to moderate. Transient injection site and systemic reactions were mitigated by methylprednisolone, paracetamol and promethazine pre-treatment. In the first part of the study BL-8040 triggered rapid and substantial mobilization of WBCs and CD34+ cells in all tested doses. 4hrs post dose, the count rose to a mean of 8, 37, 31 and 35cells/µL (placebo, 0.5, 0.75 and 1mg/kg, respectively). FACS analysis revealed substantial mobilization of immature dendritic, T, B and NK cells. In the second part the mean CD34+/kg collected were 11.6 x10⁶ cells/kg. The graft composition was rich in immune cells.</p> <p>Conclusion: 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.<br />

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