The high-affinity CXCR4 antagonist BKT140 is safe and induces a robust mobilization of human CD34+ cells in patients with multiple myeloma

Clin Cancer Res. 2014 Jan 15;20(2):469-79. doi: 10.1158/1078-0432.CCR-13-1302. Epub 2013 Nov 18.


Purpose: CXCR4 plays an important role in the retention of stem cells within the bone marrow. BKT140 (4F-benzoyl-TN14003) is a 14-residue bio stable synthetic peptide, which binds CXCR4 with a greater affinity compared with plerixafor (4 vs. 84 nmol/L). Studies in mice demonstrated the efficient and superior mobilization and transplantation of stem cells collected with GCSF-BKT140, compared with those obtained when using stem cells obtained with each one of these mobilizing agent alone. These results have served as a platform for the present clinical phase I study.

Experimental design: Eighteen patients with multiple myeloma who were preparing for their first autologous stem cell transplantation were included. Patients received a standard multiple myeloma mobilization regimen, consisting of 3 to 4 g/m(2) cyclophosphamide (day 0), followed by granulocyte colony-stimulating factor (G-CSF) at 5 μg/kg/d starting on day 5 and administered between 8 and 10 pm until the end of stem cell collection. A single injection of BKT140 (0.006, 0.03, 0.1, 0.3, and 0.9 mg/kg) was administered subcutaneously on day 10 in the early morning, followed by G-CSF 12 hours later.

Results: BKT140 was well tolerated at all concentrations, and none of the patients developed grade 3 and 4 toxicity. A single administration of BKT140 at the highest dose, 0.9 mg/kg, resulted in a robust mobilization and collection of CD34(+) cells (20.6 ± 6.9 × 10(6)/kg), which were obtained through a single apheresis. All transplanted patients received ∼5.3 × 10(6) CD34(+) cells/kg, which rapidly engrafted (n = 17). The median time to neutrophil and platelet recovery was 12 and 14 days, respectively, at the highest dose (0.9 mg/kg).

Conclusions: When combined with G-CSF, BKT140 is a safe and efficient stem cell mobilizer that enabled the collection of a high number of CD34(+) cells in 1 and 2 aphaeresis procedures, resulting in successful engraftment.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Blood Cell Count
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Synergism
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / therapy*
  • Oligopeptides / administration & dosage
  • Oligopeptides / adverse effects
  • Oligopeptides / pharmacology*
  • Protein Binding
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism
  • Treatment Outcome


  • Antineoplastic Agents
  • BKT140
  • Oligopeptides
  • Receptors, CXCR4
  • Granulocyte Colony-Stimulating Factor