Phase I Study of the Safety and Pharmacokinetics of Plerixafor in Children Undergoing a Second Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Leukemia

Ashok Srinivasan, John C. Panetta, Shane J. Cross, Asha Pillai, Brandon M. Triplett, David R. Shook, Mari H. Dallas, Christine Hartford, Anusha Sunkara, Guolian Kang, Jeffrey Jacobsen, John Choi, Wing Leung

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The safety, pharmacokinetics, and biological effect of plerixafor in children as part of a conditioning regimen for chemo-sensitization in allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is a phase I study of plerixafor designed to evaluate its tolerability at dose of .24 mg/kg given intravenously on day -4 (level 1); day -4 and day -3 (level 2); or day -4, day -3, and day -2 (level 3) in combination with fludarabine, thiotepa, melphalan, and rabbit antithymocytic globulin for a second allogeneic HSCT in children with refractory or relapsed leukemia. Immunophenotype analysis was performed on blood and bone marrow before and after plerixafor administration. Twelve patients were enrolled. Plerixafor at all 3 levels was well tolerated without dose-limiting toxicity. Transient gastrointestinal side effects of National Cancer Institute-grade 1 or 2 in severity were the most common adverse events. The area under the concentration-time curve increased proportionally to the dose level. Plerixafor clearance was higher in males and increased linearly with body weight and glomerular filtration rate. The clearance decreased and the elimination half-life increased significantly from dose level 1 to 3 (P < .001). Biologically, the proportion of CXCR4+ blasts and lymphocytes both in the bone marrow and peripheral blood increased after plerixafor administration.

Original languageEnglish (US)
Pages (from-to)1224-1228
Number of pages5
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number8
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Allogeneic
  • Children
  • Plerixafor
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Fingerprint Dive into the research topics of 'Phase I Study of the Safety and Pharmacokinetics of Plerixafor in Children Undergoing a Second Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Leukemia'. Together they form a unique fingerprint.

  • Cite this

    Srinivasan, A., Panetta, J. C., Cross, S. J., Pillai, A., Triplett, B. M., Shook, D. R., Dallas, M. H., Hartford, C., Sunkara, A., Kang, G., Jacobsen, J., Choi, J., & Leung, W. (2014). Phase I Study of the Safety and Pharmacokinetics of Plerixafor in Children Undergoing a Second Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Leukemia. Biology of Blood and Marrow Transplantation, 20(8), 1224-1228. https://doi.org/10.1016/j.bbmt.2014.04.020