Genzyme Corp. has announced that it has completed its phase 3 trial of Mozobil™ (plerixafor) in non-Hodgkin’s lymphoma (NHL), and that the trial has robustly met its primary and secondary endpoints.
The randomized, double-blind, placebo-controlled trial included 298 patients who were undergoing a hematopoietic stem cell transplant (HSCT) for NHL at medical centers in the United States and Canada. It examined the effectiveness of Mozobil in increasing the number of hematopoietic stem cells collected for a transplant.
The study compared the hematopoietic stem cell yield from patients treated with Mozobil in combination with G-CSF to patients treated with G-CSF in combination with placebo. G-CSF is the standard of care for stimulating the mobilization of stem cells from the bone marrow; Mozobil is designed to allow for the effective release of those stem cells from the marrow into the circulating blood for collection by apheresis.
In the primary efficacy endpoint, 59 percent of patients treated with a combination of Mozobil and G-CSF achieved the target threshold for collection of at least 5 million CD34+cells/kg from the peripheral blood with four or fewer days of apheresis sessions, compared with 20 percent of patients in the G-CSF/placebo group.
The three-fold increase was statistically significant in favor of the Mozobil-treated patients (p<0.0001). The 40 percent absolute difference between the two treatment groups was nearly double the target that Genzyme prospectively defined in the protocol for the study, which was reviewed by FDA as part of the Special Protocol Assessment process.
In the secondary efficacy endpoint, nearly 87 percent of patients treated with Mozobil and G-CSF achieved the minimum level of stem cells generally associated with a transplant (2 million CD34+cells/kg) in four or fewer days of apheresis sessions, compared with approximately 47 percent in the placebo arm. This result was also statistically significant in favor of the Mozobil-treated patients (p<0.0001).
The other secondary efficacy endpoints were supportive of these findings, including analysis of the number of days needed to reach target ranges for stem cell mobilization, the success of engraftment, the number of days needed to engraft, and the durability of the engraftment for the first 100 days.
Mozobil was well tolerated in the trial, with the most common adverse events being mild gastrointestinal effects and redness at the site of injection. There were two related serious adverse events seen in the Mozobil plus G-CSF arm, and one in the G-CSF plus placebo arm.
“These are very impressive results with far-reaching clinical importance for patients undergoing a stem cell transplant for lymphoma,” said Principal Investigator John F. DiPersio, M.D., Ph.D., professor, Washington University, St. Louis.
“Current literature suggests that increasing the number of stem cells in circulation and the number collected at the time of apheresis may improve the outcomes of patients undergoing a stem cell transplant, reduce the costs associated with stem cell collection and, more importantly, broaden the pool of patients for whom transplantation is an option.”