Safety, Efficacy, Pharmacokinetic and Pharmacodynamic evaluation of YF-H-2015005 for mobilizing Hematopoietic stem cells in Non-Hodgkin's Lymphoma Patients.

Background: Targeting the interaction between SDF1 and CXCR4 may provide an opportunity to intervene in the hematopoietic stem cell mobilization process. Aim: The present study aimed to investigate the safety, efficacy, pharmacokinetic and pharmacodynamic profiles of YF-H-2015005, a CXCR4 antagonist, for the mobilization of hematopoietic stem cells (HSCs). Methods: A total of 15 patients with non-Hodgkin's lymphoma (NHL) eligible for autologous hematopoietic stem cell transplantation were enrolled. All patients achieved a partial or complete remission after the first- or second-line therapy. Granulocyte colony stimulating factor (G-CSF) was given in the morning for 8 consecutive days, and 0.24 mg/kg YF-H-2015005 was subcutaneously administered in the evening of the 4th day of G-CSF treatment for up to four days. Apheresis was performed 9-10 hours following each dose of YF-H-2015005. Results: YF-H-2015005 was rapidly absorbed and eliminated, with T-max and t(1/2) of 0.5 and 5.04 +/- 1.00 hours, respectively. Moreover, the mean peripheral blood CD34(+) cell counts were elevated by 2.0- to 2.9-fold from 2 to 24 hours, and reached the maximum level of 76.5 +/- 53.9 cells/kg at 10 hours after YF-H-2015005 treatment. Fourteen (93%) out of 15 NHL patients achieved a minimum target of >= 2x10(6)/kg CD34(+) cells. Furthermore, there was no grades 3-4 treatment-related adverse event observed among these patients. Conclusion: YF-H-2015005 can serve as a safe, effective agent in combination with G-CSF for CD34(+) hematopoietic progenitor cell mobilization in NHL patients.