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

Clin Cancer Res. 2017 Nov 15;23(22):6790-6801. doi: 10.1158/1078-0432.CCR-16-2919. Epub 2017 Aug 23.


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). 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.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. Clin Cancer Res; 23(22); 6790-801. ©2017 AACR.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism*
  • Biomarkers
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Healthy Volunteers
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Immunophenotyping
  • Leukapheresis
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Animal
  • Peptides / administration & dosage*
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Transplantation, Homologous


  • 4-fluorobenzoyl-TN-14003
  • Antigens, CD34
  • Biomarkers
  • Peptides
  • Receptors, CXCR4
  • Granulocyte Colony-Stimulating Factor