A phase IV, randomized, multicenter, open-label trial comparing efficacy and systemic exposure for a standard weight-based dose versus a fixed dose of plerixafor in combination with G-CSF in patients with Non-Hodgkin\u2019s lymphoma weighing \u226470\u2009kg

John Kuruvilla,Seok Jin Kim,Yaming Su,Peter Cheverton,Jih-Luh Tang,Rita Vargo,Seok-Goo Cho,Jingyang Wu,Cheng-Hwai Tzeng

doi:10.1038/s41409-018-0253-y

Abstract

A randomized, multicenter, open-label study explored the effect of a fixed-dose (FD) of plerixafor versus the approved weight-based (WB) dose for the mobilization of hematopoietic stem cells (HSCs) in patients with non-Hodgkin’s lymphoma and a body weight of ≤70 kg. After mobilization with granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/day for 4 days, patients were randomized 1:1 to either plerixafor FD 20 mg (n = 30) or WB 0.24 mg/kg (n = 31) on the evening of Day 4. Co-primary endpoints were the proportion of patients achieving ≥5 × 106 CD34+ cells/kg in ≤4 days of apheresis, and total systemic exposure to plerixafor (area under the concentration–time curve from 0 to 10 h [AUC0–10]). There was no statistically significant difference between the proportion of patients attaining the primary efficacy endpoint (60% FD arm, 55% WB arm; P = 0.395). Exposure to plerixafor was greater in the FD arm relative to the WB arm; however, there was no appreciable difference regarding fold increases of peripheral blood CD34+ cells. The safety profile was similar between treatment groups. These results suggest there is no statistically significant difference in HSC mobilization with a standard WB dosing regimen of plerixafor plus G-CSF in patients with low body weight compared with an FD regimen.

Highlights

In patients whose B-cell or T-cell non-Hodgkin’s lymphoma (NHL) is refractory, or has relapsed after first-line therapy, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.considered the standard of care in eligible patients [1,2,3,4,5,6,7,8]
Eligibility criteria included: age 18–78 years; a biopsy confirmed diagnosis of NHL in first or second complete or partial remission following the first-line or second-line therapy, only where the first auto-HSCT was planned; body weight ≤70 kg; an Eastern Cooperative Oncology Group (ECOG) performance status ≤1; at least 4 weeks since last cycle of cancer therapy including rituximab; white blood cell count >2.5 × 109/L; absolute neutrophil count >1.5 × 109/L; and platelet count >100 × 109/L
Plerixafor plus granulocyte colony-stimulating factor (G-CSF) is approved for stem cell mobilization prior to auto-HSCT based on two phase III, randomized, double-blind, placebo-controlled, multicenter studies, which demonstrated the safety and efficacy of this combination [12, 13]

Summary

Introduction

Chemotherapy and/or cytokines have been used to mobilize peripheral blood hematopoietic stem cells (HSCs) for collection by apheresis, and the CD34+ cell count is evaluated to determine HSC content prior to transplant. Plerixafor was shown to increase the mobilization of CD34+ cells into the peripheral blood and offers a treatment option for patients undergoing stem cell mobilization for auto-HSCT. In a randomized phase II study in patients with NHL or multiple myeloma, plerixafor was well tolerated, and the combination of plerixafor and granulocyte colony-stimulating factor (G-CSF) increased the likelihood of obtaining ≥5 × 106 CD34+ cells/kg in

Methods

Results

Conclusion