Pharmacokinetics of Ch14.18 in Younger Patients With High-Risk Neuroblastoma

PRIMARY OBJECTIVES:

I. Describe the pharmacokinetics of ch14.18 (monoclonal antibody 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 GD2 levels to
identify sources of variability in the clearance.

III. Develop a pharmacokinetic model to describe the pharmacokinetic profile of ch14.18 and
derive pharmacokinetic (PK) parameters.

SECONDARY OBJECTIVES:

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 pharmacokinetic model in order to reduce
variability and simplify drug administration.

OUTLINE:

Patients undergo blood sample collection at baseline and during and after course 1, 3, or 5
of treatment for pharmacokinetic analysis. Some patients undergo blood sample collection at
baseline and during and after two treatment courses (1 and 3, 1 and 5, or 3 and 5).

Inclusion Criteria:

- Diagnosis of high-risk neuroblastoma

- Enrolled on the COG protocol ANBL0032 or ANBL0931 and eligible to receive ch14.18
according to the criteria on these primary treatment protocols

- Parental informed consent and verbal assent of the subject when appropriate

Exclusion Criteria:

- Prior testing demonstrating the presence of HACA

- Anaphylactic reaction to ch14.18 on a prior treatment cycle