Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma.
OBJECTIVE
This study evaluates the safety and efficacy of plerixafor (AMD3100), a CXCR4 antagonist, in mobilizing hematopoietic stem cells for autologous stem-cell transplantation in non-Hodgkin's lymphoma (NHL) patients.


METHODS
This is a phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with non-Hodgkin's lymphoma requiring an autologous hematopoietic stem-cell transplantation in first or second complete or partial remission were eligible. Patients received granulocyte colony-stimulating factor (G-CSF; 10 microg/kg) subcutaneously daily for up to 8 days. Beginning on evening of day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 microg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until > or = 5 x 10(6) CD34+ cells/kg were collected. The primary end point was the percentage of patients who collected > or = 5 x 10(6) CD34+ cells/kg in 4 or fewer apheresis days.


RESULTS
This report presents all data for all patients (n = 298) through 12 months follow-up. Eighty-nine (59%) of 150 patients in the plerixafor group and 29 (20%) of 148 patients in the placebo group met the primary end point (P < .001). One hundred thirty-five patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation after initial mobilization. Median time to engraftment was similar in both groups. The most common plerixafor-associated adverse events were GI disorders and injection site reactions.


CONCLUSIONS
Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34+ cell target for transplantation in fewer apheresis days, compared with G-CSF alone.
DiPersio
John F
JF
Washington University School of Medicine, St Louis, MO, USA. jdipersi@im.wustl.edu
Micallef
Ivana N
IN
Stiff
Patrick J
PJ
Bolwell
Brian J
BJ
Maziarz
Richard T
RT
Jacobsen
Eric
E
Nademanee
Auayporn
A
McCarty
John
J
Bridger
Gary
G
Calandra
Gary
G
D000328:Adult; D000368:Aged; D001596:Benzylamines; D000080027:Cyclams; D003967:Diarrhea / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006261:Headache / Q000209:etiology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006801:Humans; D055104:Infusions, Subcutaneous; D053208:Kaplan-Meier Estimate; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D011446:Prospective Studies; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor