Yf-H-2015005, a New CXCR4 Antagonist, in the Mobilization of Hematopoietic Stem Cells in Patients with Non-Hodgkin Lymphoma: A Randomized-Controlled Phase 3 Study

Background:

Autologous hematopoietic stem cell transplantation (AHSCT) is an important therapy for non-Hodgkin's lymphoma (NHL). This study evaluated the safety and efficacy of YF-H-2015005, a new CXCR4 antagonist, when used to mobilize hematopoietic stem cells in patients with NHL eligible for treatment with AHSCT.

Methods:

This phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study enrolled patients (age range, 18 to 65 years) with NHL, and who were in their first or second complete or partial remission. The patients received granulocyte colony-stimulating factor (G-CSF, 10 mg/kg/day) each morning for up to 8 days. Treatment with YF-H-2015005 (0.24 mg/kg/day) or placebo was initialed during the evening of the fourth day of G-CSF administration, and then continued for up to 4 days. Starting on day 5, apheresis was performed for 9 to 10 hours after each dose of YF-H-2015005 or until ≥ 5 × 10⁶ CD34⁺ cells/kg had been collected. The primary endpoint was the percentage of patients who collected ≥ 5 × 10⁶ CD34+ cells/kg during the course of 4 or fewer apheresis days. The secondary endpoints were the percentage of patients who collected ≥ 2 × 10⁶ CD34⁺ cells/kg during the course of 4 or fewer apheresis days, the number of apheresis days required to reach ≥ 2 × 10⁶ CD34⁺ cells/kg, the number of apheresis days required to reach ≥ 5 × 10⁶ CD34⁺ cells/kg, and patient safety.

Results:

A total of 101 patients with NHL were randomly assigned to the YF-H-2015005 group (n = 51or placebo group (n = 50), respectively. The percentage of patients who met the primary endpoint was 57% (29/51) in the YF-H-2015005 group and 12% (6/50) in the placebo group (P < 0.001). A larger proportion of patients in the YF-H-2015005 group (86%) achieved the secondary endpoint of collecting ≥ 2 × 10⁶ CD34⁺ cells/kg in 4 or fewer apheresis days when compared with the placebo group (38%, P < 0.001). Patients in the YF-H-2015005 group required shorter time periods to collect ≥ 2 × 10⁶ CD34⁺ cells/kg (1 days vs. 4 days) and ≥ 5 × 10⁶ CD34⁺ cells/kg (3 days vs. not reached). Treatment-related adverse event were observed in 37 patients (20 in the YF-H-2015005 group and 17 in the placebo group). The most common adverse events in the YF-H-2015005 group were diarrhea (14%), hyperhidrosis(6%), elevated alkaline phosphatase (6%). No serious treatment-related adverse event occurred.

Conclusions:

The combination of YF-H-2015005 and G-CSF was a tolerable regimen for use in rapidly mobilizing and collecting CD34⁺ cells for transplantation in patients with NHL.