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.
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.
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee. Electronic address: ashok.srinivasan@stjude.org.
Ashok
A
Srinivasan
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
John C
JC
Panetta
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
Shane J
SJ
Cross
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
Asha
A
Pillai
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
Brandon M
BM
Triplett
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
David R
DR
Shook
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
Mari H
MH
Dallas
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Christine
C
Hartford
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Anusha
A
Sunkara
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Guolian
G
Kang
Department of Pathology, Phoenix Children's Hospital, Phoenix, Arizona.
Jeffrey
J
Jacobsen
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
John
J
Choi
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
Wing
W
Leung
D001596:Benzylamines; D054316:Biomarkers, Pharmacological; D000080027:Cyclams; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D012008:Recurrence; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D001596:Benzylamines; D054316:Biomarkers, Pharmacological; D000080027:Cyclams; D006571:Heterocyclic Compounds; C088327:plerixafor
Allogeneic; Children; Plerixafor; Stem cell transplantation