NCT01704872

ch14.18/CHO Bridging Study

Bridging Study Using ch14.18/CHO Antibody in Children With Refractory Neuroblastoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: St. Anna Kinderkrebsforschung · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the safety, pharmacokinetic and activity profiles of the ch14.18 antibody produced in cells of hamster origin (ch14.18/CHO).

Detailed description

Anti-ganglioside GD2 antibody ch14.18 is a monoclonal antibody specifically recognizing the target antigen GD2, which is expressed on virtually all neuroblastoma tumours. This antibody is a chimeric protein and consists to 30% of mouse variable light and heavy chain and to 70% of human constant heavy and light chain. Ch 14.18 has already been tested in stage 4 neuroblastoma patients in phase I/II clinical trials with encouraging response rates. Therefore, the European SIOP neuroblastoma group designed a Phase III protocol to test the efficacy of ch14.18 immunotherapy in a randomised trial. However, the ch14.18 antibody for this Phase III trial was recloned and produced in Chinese hamster ovary (CHO) cells in contrast to ch14.18 antibody used for previous clinical trials, which was produced in murine, non-secreting myeloma cells (SP2/0). Although the antibody-gene transfer into CHO and SP2/0 was done with exactly the same plasmid assuring an identical protein sequence, changes in the glycosylation of the final protein product may occur since the glycosylation pattern varies between different production cell lines. Glycosylation is important for the immunological effector function of the antibody and the pharmacokinetics in patients. Therefore, this change is considered to be a major change in production requiring the reassessment of the new product in a Phase I clinical trial. The primary objective of this trial is the re-evaluation of toxicity of the new ch14.18/CHO antibody. This is ultimately followed by the secondary objectives including the determination of pharmacokinetics and immunostimulation in patients receiving ch14.18/CHO therapy. This involves particularly the determination of activation of immune effector cells and complement during and after application of ch14.18/CHO. Subsequently, we will evaluate the clinical effect of this treatment on the course of the disease. The nature of this phase I trial is a bridging study for a medicinal product subjected to a major change in production according to the guidelines provided by the "Committee for Proprietary Medicinal Products" (CPMP) of the "European Agency for the Evaluation of Medicinal Products (EMEA) (Document Number CPMP/BWP/3207/00).

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	ch14.18/CHO

Timeline

• Start date: 2005-07-01
• Primary completion: 2006-02-01
• Completion: 2012-03-01
• First posted: 2012-10-12
• Last updated: 2020-10-22

Locations

3 sites across 3 countries: Austria, Germany, Italy