ch14.18/CHO Bridging Study
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01704872|
Recruitment Status : Completed
First Posted : October 12, 2012
Last Update Posted : October 12, 2012
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Drug: ch14.18/CHO||Phase 1|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Bridging Study Using ch14.18/CHO Antibody in Children With Refractory Neuroblastoma|
|Study Start Date :||July 2005|
|Actual Primary Completion Date :||February 2006|
|Actual Study Completion Date :||March 2012|
Experimental: dose level finding ch14.18/CHO
A dose escalation design based on Phase I rules starting at 10 mg/m2/day ch14.18/CHO. This is 50% below the dose of ch14.18/SP2/0 used in a large cohort of patients. Dose escalation will be adapted to a modified Fibonacci series aiming at 10, 20 and 30 mg/m2 of ch14.18/CHO. Since this study is a bridging study aiming at a reassessment of the toxicity and determination of the pharmacokinetics of ch14.18/CHO, only a limited number of dose escalation steps (3) is implemented in the design.
Other Name: Chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary cells
- Adverse events as a measure of safety/tolerability [ Time Frame: 4 weeks (end of cycle 1) ]Reassess the toxicity profile of one treatment cycle with ch14.18 recloned in CHO cells (ch14.18/CHO), when administered as daily eight-hour infusions and accompanied by supportive care measures in particular to prevent pain, fever and allergic reactions according to previously established standards.
- Measure ch14.18/CHO levelsDetermine the pharmacokinetics of the ch14.18/CHO antibody
- Systemic immune modulationDetermine whether systemic immune modulation results from this therapy using ch14.18/CHO antibody by measuring activation of humoral and cellular immune system.
- ch14.18/CHO immunogenicityDetermine the immunogenicity of ch14.18/CHO antibody by measuring human anti-chimeric humoral immune response.
- Anti-tumour responseEvaluate anti-tumour responses resulting from this treatment regimen through clinical assessments in patients with measurable disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01704872
|St Anna Kinderspital|
|Vienna, Austria, 1090|
|Charite Children's Hospital|
|Berlin, Germany, 13353|
|Gaslini Children's Hospital|
|Genova, Italy, 16147|
|Principal Investigator:||Holger Lode, MD||Charite Children's Hospital|
|Principal Investigator:||Ruth Ladenstein, MD||St. Anna Kinderkrebsforschung|