期刊
CLINICAL CANCER RESEARCH
卷 23, 期 22, 页码 6790-6801出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-16-2919
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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). 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 (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. Results: BL-8040 was found safe and well tolerated at all doses tested (0.5-1 mg/kg). Themain 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/mL (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 x 10(6) cells/kg. The graft composition was rich in immune cells. Conclusions: 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. (C) 2017 AACR.
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