Pharmacokinetics of the Chimeric Anti-GD2 Antibody, ch14.18, in Children With High-Risk Neuroblastoma
I. Describe the pharmacokinetics (PKs) of monoclonal antibody Ch14.18 (Ch14.18) in children
with high-risk neuroblastoma.
II. Quantify the degree of inter-patient and intra-patient variability in the clearance of
Ch14.18, and correlate Ch14.18 clearance with patient characteristics, the presence of human
anti-chimeric antibody (HACA), tumor burden (assessed on scans), and plasma G_D2 levels to
identify sources of variability in the clearance.
III. (Exploratory) Develop a PK model to describe the PK profile of Ch14.18 and derive PK
I. Correlate plasma concentrations of Ch14.18 with the severity of neuropathic pain, which
is being quantified using an observational pain scale, and the total dose of morphine
administered to control pain.
II. Develop a limited-sampling strategy that will accurately quantify the area under the
curve (AUC) of Ch14.18.
III. Simulate alternative dosing strategies with the PK model in order to reduce variability
and simplify drug administration.
Patients undergo blood sample collection at baseline and during and after course 1, 3, or 5
of monoclonal antibody Ch14.18 (Ch14.18) and sargramostim for pharmacokinetic, human
anti-chimeric antibody, and concentration of ganglioside G_D2 studies. The Ch14.18A level is
measured via ELISA. A pharmacokinetic model is then developed using the Modeling Laboratory
Parents, guardians, or caretakers are asked to assess patients' pain three times a day,
prior to, during, and at the end of Ch14.18 treatment.
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
PK parameters of Ch14.18 in children with high‐risk neuroblastoma during and after 4 daily 10‐hour infusions, including the peak concentration, trough concentration, AUC, clearance, volume of distribution, half-life, and mean residence time
PK parameters will be derived from the plasma concentration-time data. A one-compartment model fit to the concentration-time data will estimated the volume of distribution and the first order elimination rate constant, which will in turn be used to calculate clearance, half-life, AUC0-infinity, AUC0-last, and the mean residence time. An error function and the dependency for each fitted parameter will be reported.
Before and after infusion on days 3-5; before, after, and 4-6 hours after infusion on day 6; 12-14 hours after infusion on day 7; on the morning of days 10, 14, 17, and 24; and before infusion on day 31
Children's Hospital of Philadelphia
United States: Food and Drug Administration
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