A single-center, open-label clinical study to evaluate pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte stimulating factor in pediatric patients with acute lymphoblastic leukemia.

Abstract

e22501 Background: The aims of the study were to investigate the pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony stimulating factor(PEG-rhG-CSF) in pediatric patients with acute lymphoblastic leukemia(ALL), and compare the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) and rhG-CSF. Methods: Pediatric patients with newly diagnosed ALL who planned to use CAM (cyclophosphamide, cytarabine, 6-mercaptopurine) for chemotherapy were assigned to PEG-rhG-CSF group or rhG-CSF group. In the PEG-rhG-CSF group, PEG-rhG-CSF (100ug/kg) was injected subcutaneously once 48 hours after chemotherapy. In the rhG-CSF group, rhG-CSF (150ug/d) was injected subcutaneously daily from 48 hours after chemotherapy until the absolute neutrophil count (ANC) was≥1.0×109/L. The serum concentration of PEG-rhG-CSF was detected by enzyme-linked immunosorbent assay (ELISA). Safety and efficacy of the two groups were evaluated. Results: Between November 2015 to April 2016, 17 pediatric patients were assigned to PEG-rhG-CSF(n = 9) or rhG-CSF(n = 8) groups. The main pharmacokinetic parameters (mean±SD) of PEG-rhG-CSF group were as follows: Cmax was 353.50±136.3 ng/ml, Tmax was 44.00±20.8 h, t1/2 was 14.58± 2.2h. The PEG-rhG-CSF serum concentration and ANC curve were consistent with the mechanism of neutrophil mediated clearance. The average value of ANC nadir in PEG-rhG-CSF group was 0.18 (±0.32)×109/L, and the rhG-CSF group was 0.08 (±0.09)×109/L, there was no significant difference between the two groups ( P = 0.469). Compared with rhG-CSF, the average time of ANC recovery in PEG-rhG-CSF group was earlier (18.33±2.18 vs. 21.50±2.33, P = 0.021). There were no significant differences in the incidence of FN and infection, the duration of grade Ⅳ neutropenia and hospitalization, and the safety of the two groups. Conclusions: PEG-rhG-CSF had favorable efficacy in pediatric patients with ALL receiving chemotherapy, and there was no serious adverse event. Compared with rhG-CSF, PEG-rhG-CSF needed only once in each chemotherapy cycle, which is more suitable for pediatric patients. Clinical trial information: NCT02953730.