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NeuroblastomaPhase 2NCT02743429

Phase II Study of Monoclonal Antibody ch14.18/CHO Continuous Infusion in Patients With Primary Refractory or Relapsed Neuroblastoma

A Phase 2 study testing dinutuximab beta in people with Neuroblastoma, run by University Medicine Greifswald at 2 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In this trial, monoclonal anti-Disialoganglioside GD2 (GD2) antibody ch14.18/CHO will be assessed for the treatment of patients with relapsed or refractory neuroblastoma. The antibody is used as a single agent applied in a new treatment schedule associated with less side effects. 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?
dinutuximab beta
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesin 2 countries
Study dates
27 Mar 2015to Jun 2024
Phase
Phase 2
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

  • ≥ 12 months and ≤ 21 years of age at the time of study entry
  • Diagnosis of neuroblastoma according to the INSS criteria
  • Tumour burden controlled by conventional therapy (except patients with early minimal bone marrow relapse) fulfilling one of the following criteria:
  • Primary refractory patients with stage 4 disease
  • Relapse after primary stage 4 disease
  • Disseminated relapse after primary localized neuroblastoma.
Show all 29Show fewer
  • Measurable and/or evaluable disease in any of the following sites (skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site and/or bone marrow) as measured by mIBG scan, CT, MRI and/or immunocytology
  • Life expectancy of at least 12 weeks.
  • Performance status greater or equal to 70% (Lansky Score or Karnofsky)
  • Consent to the placement of a central venous line, if one has not already been placed
  • Off any standard or experimental treatment for at least two weeks prior to start of immunotherapy (Day 1 of cycle 1) and fully recovered from the short-term major toxic effects
  • No immediate requirements for palliative chemotherapy, radiotherapy or surgery
  • At least 2 weeks from any tumour surgery and fully recovered from any post-surgical complications
  • HIV sero-negative
  • Neither active nor chronic-replicative Hepatitis B infection
  • Females of childbearing potential must have a negative pregnancy test and must agree to use an effective birth control method during the whole study duration including the last FU visit.
  • Female patients who are lactating must agree to stop breast-feeding.
  • Patient may have had prior CNS metastases, provided the following criteria are all met:
  • 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).
  • The patient is off steroids for four weeks prior to starting trial treatment and will not require them during the course of the study.
  • Patients with seizure disorders may be enrolled if well controlled on anticonvulsants and if no seizures have occurred within a 6 week period prior to starting trial treatment
  • All patients and/or their parents or legal guardians must sign a written informed consent.
  • Laboratory testing:
  • Shortening fraction of ≥ 30% on Echocardiogram.
  • FEV1 and FVC > 60% of the predicted by pulmonary function tests. Children unable to do PFTs should have no dyspnoea at rest and a pulse oximetry > 94% in room air.
  • Adequate bone marrow function as defined by ANC >0.5 10^9/L, platelets ≥ 20 10^9/L and haemoglobin > 8.0 g/dL
  • Adequate liver function, as defined by an ALT or AST < 5 x normal and a total bilirubin < 1.0 mg/dL.
  • Adequate renal function, as defined by a serum creatinine <1.5 mg/dL or a creatinine clearance or radioisotope GFR of > 60 mL/minute/1.73 m².

Who cannot join

  • Progressive disease at the time of inclusion into the study.
  • ADA positivity due to previous treatment with an anti-GD2 antibody (e.g. ch14.18/SP2/0, ch14.18/CHO).
  • Previous treatment with ch14.18/CHO in this study.
  • Requirement, or likely requirement, for corticosteroids or other immunosuppressive drugs.
  • Concurrent treatment with any non-trial anticancer therapies. g) Patients with hypersensitivity against one component of the investigational product or against mouse proteins.
  • Female patients of childbearing potential if 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.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Austria1 site

  • St. Anna Kinderkrebsforschung e.V. CHILDREN'S CANCER RESEARCH INSTITUTE

    Vienna, 1090

Other trials in Austria

Germany1 site

  • University Medicine Greifswald

    Greifswald, 17475

Other trials in Germany

About this study

In this trial, monoclonal anti-Disialoganglioside GD2 (GD2) antibody ch14.18/CHO will be assessed for the treatment of patients with relapsed or refractory neuroblastoma. The antibody is used as a single agent applied in a new treatment schedule associated with less side effects.

Read the detailed description

The Treatment with ch14.18 antibody has demonstrated efficacy in patients with neuroblastoma. However the treatment is associated with an on target side effect, i.e. neuropathic pain. This requires coadministration of intravenous morphine.

In this clinical Trial we will evaluate a less toxic treatment regimen consisting of continuous longterm Infusion (LTI) of ch14.18/CHO administered at a dose of 10 mg/m2/day over 10 days (total dose 100 mg/m2/cycle). Patients may receive up to five 35-day cycles in absence of signs of progression.

Conditions
Neuroblastoma
Being tested
dinutuximab beta
Keywords
ch14.18/CHO, neuroblastoma, long term infusion
Medical subject headings
Neuroblastoma

What participants receive

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

  • dinutuximab betaDrug

    Up to 5 cycles of continuous infusion of ch14.18/CHO is administered at a dose of 10 mg/m2/day over 10 days (total dose 100 mg/m2/cycle).

    Cycle duration: 35-days.

Study groups in NCT02743429
Study groupRoleWhat they receive
Long term infusion of ch14.18/CHOExperimental10 day continuous Infusion of ch14.18/CHO.
Receives: Drug: dinutuximab beta

What is being measured

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

  1. Anti-tumour activity of ch14.18/CHO continuous infusion

    The response rate in patients with measurable/evaluable disease (skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site and bone marrow) as measured by Metaiodobenzylguanidine scan (MIBG), Computed tomography (CT), Magnetic Resonance Imaging (MRI) and/or immunocytology at the end of the study.

    Measured: 2 years

Secondary outcomes (14)

  1. Progression-Free Survival

    Measured: 5 years

  2. Safety and tolerability

    • Pain intensity and the need for appropriate medication for pain relief
    • Adverse events, vital signs and changes in clinical laboratory assessments

    Measured: 2 years

  3. Immunogenicity

    Immunogenicity: Anti-Drug Antibody (ADA)

    Measured: 2 years

  4. Immunophenotyping

    Unit: cells/µl

    Measured: 2 years

  5. Antibody dependent cellular cytotoxicity (ADCC)

    Unit: %

    Measured: 2 years

  6. Complement dependent cytotoxicity (CDC)

    Unit: %

    Measured: 2 years

  7. Whole Blood Test (WBT)

    Unit: %

    Measured: 2 years

  8. Cytokines

    Unit: µg/ml

    Measured: 2 years

  9. Clearance (CL)

    Unit: l/d*m²

    Measured: 2 years

  10. Volume distribution at steady state (Vdss)

    Unit: l/m²

    Measured: 2 years

  11. mean residence time (MRT)

    Unit: days

    Measured: 2 years

  12. half-life time (t1/2)

    Unit: days

    Measured: 2 years

  13. Area Under the Curve (AUC)

    Unit: µg*d/ml

    Measured: 2 years

  14. Maximum Plasma Concentration (Cmax) and Minimum Plasma Concentration (Cmin)

    Unit: µg/ml

    Measured: 2 years

Timeline

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

  1. First posted19 Apr 2016 (estimated)
  2. Study start27 Mar 2015
  3. Primary completionDec 2023 (estimated)
  4. Study completionJun 2024 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02743429
Sponsor's protocol ID
APN311-304
Other IDs
2014-000588-42, 2014
Status last verified
Oct 2021
First submitted
18 Mar 2016
Last updated
4 Oct 2021
Results posted
No
Data monitoring committee
No

Publications

  • Lode HN, Ehlert K, Huber S, Troschke-Meurer S, Siebert N, Zumpe M, Loibner H, Ladenstein R. Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study. Br J Cancer. 2023 Nov;129(11):1780-1786. doi: 10.1038/s41416-023-02457-x. Epub 2023 Oct 10.

    PubMed 37813959

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing dinutuximab beta in people with Neuroblastoma, run by University Medicine Greifswald at 2 sites in 2 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 29 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Austria, Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

Anti-tumour activity of ch14.18/CHO continuous infusion (time frame: 2 years). 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 NCT02743429, which also lists 1 linked publication.

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 4 Oct 2021.

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