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NeuroblastomaPhase 1NCT01704872

ch14.18/CHO Bridging Study

A Phase 1 study testing ch14.18/CHO in people with Neuroblastoma, run by St. Anna Kinderkrebsforschung at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 1 year to 21 years
Conditions the study is for
Neuroblastoma
What is being tested?
ch14.18/CHO
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
3 sitesin 3 countries
Study dates
Jul 2005to Mar 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must be <= 21 years of age.
  • Patients must be diagnosed with neuroblastoma according to the INSS criteria.
  • Disease must be considered refractory to conventional therapy including patients:
  • over 1 year of age and presenting as stage 4 disease which have been refractory to first line chemotherapy
  • over 1 year with recurrent disease after multi-agent chemotherapy (including any stage and biological pattern)
  • If the patient history meets the above criteria, any disease states except overt progressing disease at the time of antibody treatment renders the patients eligible for this study.
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  • Patients may not have developed human anti-chimeric antibody due to pre-treatment with ch14.18/SP2/0.
  • Patients must have a performance status greater or equal 70% (Lansky Score).
  • Patients must have an estimated life expectancy of at least 12 weeks.
  • Patients must consent to the placement of a central venous line (Broviac or Hickman catheter), if one has not already been placed, or a stable IV anticipated to last for the 5 days required to administer the 5 infusions each month
  • Patients must have fully recovered the toxic effects of any prior therapy.
  • Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.
  • Patients may have had prior CNS metastasis providing, the patient's CNS disease has been previously treated, the patient's CNS disease has been clinically stable for four weeks prior to starting this study (assessment must be made clinically and by CT or MRI scan), and the patient is off steroids for CNS disease for four weeks prior to starting on study and during the course of the study. Patients with seizure disorders may be enrolled if on anti-convulsants and are well controlled.
  • Patients should have a shortening fraction of >= 27% by Echocardiogram or ejection function of >50% by gated radionuclide study.
  • Patients should have FEV1 and FVC >60% of predicted by pulmonary function tests. Children unable to do PFTs should have no dyspnea at rest and a pulse oximetry >94% on room air.
  • All patients must have adequate bone marrow function as defined by ANC >1000/uL, platelets >= 75,000/uL and haemoglobin >= 9.0 gm/dL. Transfusions are permitted to meet these platelet and haemoglobin criteria.
  • Patients must have adequate liver function, as defined by an ALT or AST < 5 x normal and a total bilirubin < 1.0 mg/dL.
  • Patients must have adequate renal function, as defined by a serum creatinin <= 1.5 mg/dL or a creatinin clearance or radioisotope GFR of >= 60 mL/minute.
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional and national requirements for human studies must be met.

Who cannot join

  • Patients who have received chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapy within three weeks prior to study.
  • Females of childbearing potential will be excluded if they are pregnant, nursing, or not using effective contraception during the treatment period, as the potential effects of ch14.18 on the fetus have not been determined.
  • Patients with significant intercurrent illnesses
  • Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.
  • Patients with significant psychiatric disabilities or uncontrolled seizure disorders.
  • Patients with active infections or active peptic ulcer, unless these conditions are corrected or controlled.
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  • Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade >= 2) are ineligible.
  • Patients with clinically significant, symptomatic, pleural effusions.
  • Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs for intercurrent disease.
  • Patients who have had major surgery, i.e. laparotomy or thoracotomy) within the past two weeks.
  • Patients with organ allografts, including bone marrow or haematopoietic stem cells. Patients receiving prior autologous bone marrow or stem cell reinfusions are eligible.
  • Patients must be tested for HIV and Hepatitis B Surface (HBS) Ag and excluded, if positive, as this may influence the ability of the immune system to be stimulated by this treatment.

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Austria1 site

  • St Anna Kinderspital

    Vienna, 1090

Other trials in Austria

Germany1 site

  • Charite Children's Hospital

    Berlin, 13353

Other trials in Germany

Italy1 site

  • Gaslini Children's Hospital

    Genova, 16147

Other trials in Italy

About this study

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

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).

Read the 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
Being tested
ch14.18/CHO
Keywords
Neuroblastoma, Refractory neuroblastoma, ch14.18/CHO
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ch14.18/CHODrug

    Also called Chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary cells

Study groups in NCT01704872
Study groupRoleWhat they receive
dose level finding ch14.18/CHOExperimentalA 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.
Receives: Drug: ch14.18/CHO

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events as a measure of safety/tolerability

    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.

    Measured: 4 weeks (end of cycle 1)

Secondary outcomes (4)

  1. Measure ch14.18/CHO levels

    Determine the pharmacokinetics of the ch14.18/CHO antibody

  2. Systemic immune modulation

    Determine whether systemic immune modulation results from this therapy using ch14.18/CHO antibody by measuring activation of humoral and cellular immune system.

  3. ch14.18/CHO immunogenicity

    Determine the immunogenicity of ch14.18/CHO antibody by measuring human anti-chimeric humoral immune response.

  4. Anti-tumour response

    Evaluate anti-tumour responses resulting from this treatment regimen through clinical assessments in patients with measurable disease

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2012 (estimated)
  2. Study startJul 2005
  3. Primary completionFeb 2006
  4. Study completionMar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01704872
Sponsor's protocol ID
SIOPENRNET001
Other IDs
2005-001267-63, 2005
Status last verified
Oct 2020
First submitted
8 Oct 2012
Last updated
22 Oct 2020
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ch14.18/CHO in people with Neuroblastoma, run by St. Anna Kinderkrebsforschung at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Austria, Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events as a measure of safety/tolerability (time frame: 4 weeks (end of cycle 1)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01704872.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.

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