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. 2020 Jul 25;11(19):5635-5640.
doi: 10.7150/jca.48748. eCollection 2020.

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

Weiping Liu  1 , Yan Xie  1 , Lingyan Ping  1 , Min Jiang  2 , Guanmin Zhang  3 , Yimin Cui  4 , Junyu Xu  4 , Meng Wu  1 , Xin Leng  1 , Xiaopei Wang  1 , Shufang Wang  5 , Jun Zhu  1 , Yuqin Song  1
Affiliations

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

Weiping Liu et al. J Cancer. .

Abstract

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 Tmax and t1/2 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 ≥2×106/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.

Keywords: Drug Evaluation; Hematopoietic Stem Cell Mobilization; Lymphoma, Non-Hodgkin's; Pharmacokinetics; Safety.

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Conflict of interest statement

Competing Interests: Shufang Wang is an employee of Hefei Yifan Biopharmaceuticals Inc. The other authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Structural formula of YF-H-2015005.
Figure 2
Figure 2
Mean plasma concentrations of YF-H-2015005 over time as expressed on linear (A) and semilogarithmic (B) scales.
See this image and copyright information in PMC

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