Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC)

Bruce Morland,C Michel Zwaan,C Michel Zwaan,Tomas Kepak,Qianying Liu,Sandro Dallorso,Isaac Yaniv,Jochen Rößler,Eileen Doyle,Julian Sevilla,Jochen Rößler,Peter Bader,Peter Bader,Gergely Kriván,Roberto Luksch,Gianni Bisogno,Sandro Dallorso,Britta Maecker-Kolhoff,Isaac Yaniv,Peter Lang,Dermot Murphy,John Bernard,David Sumerauer,Franco Locatelli,Franco Locatelli,Franco Locatelli

doi:10.1038/s41409-020-0836-2

Abstract

This study (NCT01288573) investigated plerixafor’s safety and efficacy in children with cancer. Stage 1 investigated the dosage, pharmacokinetics (PK), pharmacodynamics (PD), and safety of plerixafor + standard mobilization (G-CSF ± chemotherapy). The stage 2 primary endpoint was successful mobilization (doubling of peripheral blood CD34+ cell count in the 24 h prior to first apheresis) in patients treated with plerixafor + standard mobilization vs. standard mobilization alone. In stage 1, three patients per age group (2–<6, 6–<12, and 12–<18 years) were treated at each dose level (160, 240, and 320 µg/kg). Based on PK and PD data, the dose proposed for stage 2 was 240 µg/kg (patients 1–<18 years), in which 45 patients were enrolled (30 plerixafor arm, 15 standard arm). Patient demographics and characteristics were well balanced across treatment arms. More patients in the plerixafor arm (24/30, 80%) met the primary endpoint of successful mobilization than in the standard arm (4/14, 28.6%, p = 0.0019). Adverse events reported as related to study treatment were mild, and no new safety concerns were identified. Plerixafor + standard G-CSF ± chemotherapy mobilization was generally well tolerated and efficacious when used to mobilize CD34+ cells in pediatric cancer patients.

Highlights

Plerixafor (Mozobil®, Sanofi, Cambridge, MA, USA) is an antagonist of the 7 transmembrane G protein coupled chemokine (C-X-C motif) receptor 4 (CXCR4) that works by disrupting the interaction of CXCR4 with stromal cellderived factor-1, resulting in the release of CD34+ stem cells into the circulation [1,2,3,4]
In the United States, plerixafor is licensed for use in combination with granulocyte colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) into peripheral blood (PB) for collection and subsequent autologous HSC transplantation (HSCT) in adult patients with non-Hodgkin lymphoma or multiple myeloma (MM)
This study investigated the appropriate dosing, safety, and efficacy of plerixafor when given in combination with G-CSF, in pediatric patients with different types of cancer

Summary

Introduction

Plerixafor (Mozobil®, Sanofi, Cambridge, MA, USA) is an antagonist of the 7 transmembrane G protein coupled chemokine (C-X-C motif) receptor 4 (CXCR4) that works by disrupting the interaction of CXCR4 with stromal cellderived factor-1, resulting in the release of CD34+ stem cells into the circulation [1,2,3,4]. In the United States, plerixafor is licensed for use in combination with granulocyte colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) into peripheral blood (PB) for collection and subsequent autologous HSC transplantation (HSCT) in adult patients with non-Hodgkin lymphoma or multiple myeloma (MM). In the European Union, plerixafor is indicated for use in combination with G-CSF to enhance mobilization of HSCs into PB and subsequent autologous HSCT in adults with lymphoma and MM, who are proven to be poor mobilizers. While the efficacy and safety of plerixafor is well established in adults, limited data for its use in children are available. This study investigated the appropriate dosing, safety, and efficacy of plerixafor when given in combination with G-CSF, in pediatric patients with different types of cancer

Methods

Results

Conclusion