J Cancer 2020; 11(19):5635-5640. doi:10.7150/jca.48748

Research Paper

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

Weiping Liu1, Yan Xie1, Lingyan Ping1, Min Jiang2, Guanmin Zhang3, Yimin Cui4, Junyu Xu4, Meng Wu1, Xin Leng1, Xiaopei Wang1, Shufang Wang5, Jun Zhu1, Yuqin Song1✉

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, No.52 Fucheng Road, Haidian District, Beijing 100142, China.
2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), National Drug Clinical Trial Center (GCP Center), Peking University Cancer Hospital & Institute, No.52 Fucheng Road, Haidian District, Beijing 100142, China.
3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, No.52 Fucheng Road, Haidian District, Beijing 100142, China.
4. Peking University First Hospital, Department of Pharmacy, No.8 Xishiku Street, Xicheng District, Beijing 100034, China.
5. Hefei Yifan Biopharmaceuticals Inc., Intersection between Jinxiu avenue and qinglongtan road, Hefei 610000, China.

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Citation:
Liu W, Xie Y, Ping L, Jiang M, Zhang G, Cui Y, Xu J, Wu M, Leng X, Wang X, Wang S, Zhu J, Song Y. Safety, Efficacy, Pharmacokinetic and Pharmacodynamic evaluation of YF-H-2015005 for mobilizing Hematopoietic stem cells in Non-Hodgkin's Lymphoma Patients. J Cancer 2020; 11(19):5635-5640. doi:10.7150/jca.48748. Available from http://www.jcancer.org/v11p5635.htm

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