Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-001828-22
    Sponsor's Protocol Code Number:101
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-01-12
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedDenmark - DHMA
    A.2EudraCT number2017-001828-22
    A.3Full title of the trial
    A Multicenter Phase 2/3 Trial of the Efficacy and Safety of Intracerebroventricular Radioimmunotherapy using 131I-omburtamab for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial in several sites where pediatric patients with Neuroblastoma are treated with injections of 131I-omburtamab (the study drug). The tolerability and efficacy of the drug will be tested.
    A.4.1Sponsor's protocol code number101
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03275402
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/322/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorY-mAbs Therapeutics A/S
    B.1.3.4CountryDenmark
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportY-mAbs Therapeutics A/S
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKLIFO A/S
    B.5.2Functional name of contact pointVice President, Clinical
    B.5.3 Address:
    B.5.3.1Street AddressSmedeland 36
    B.5.3.2Town/ cityGlostrup
    B.5.3.3Post code2600
    B.5.3.4CountryDenmark
    B.5.4Telephone number+4544222935
    B.5.6E-mailKlas.Raadberg@klifo.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1839
    D.3 Description of the IMP
    D.3.1Product name131I-omburtamab
    D.3.2Product code 131I-murine 8H9
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntracerebroventricular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNomburtamab
    D.3.9.1CAS number 1895083-75-6
    D.3.9.2Current sponsor code131I-omburtamab
    D.3.9.3Other descriptive nameOMBURTAMAB
    D.3.9.4EV Substance CodeSUB188981
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0.3 to 1.4
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product Yes
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment of pediatric neuroblastoma patients with CNS relapse as evidenced by CNS/LM metastases
    E.1.1.1Medical condition in easily understood language
    Treatment of pediatric neuroblastoma patients with CNS relapse as evidenced by CNS/LM metastases
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10073130
    E.1.2Term Central nervous system neuroblastoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate overall survival (OS) rate at 3 years
    E.2.2Secondary objectives of the trial
    1. To evaluate CNS/LM progression-free survival (CNS/LM PFS) at 6 and 12 months
    2. To evaluate Overall Survival (OS) at 12 months
    3. To evaluate the objective response rate (ORR) at 6 months
    4. To evaluate dosimetry of 131I-omburtamab
    5. To evaluate the pharmacokinetics of 131I-omburtamab
    6. To evaluate safety of 131I-omburtamab
    7. To evaluate the immunogenicity of 131I-omburtamab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients must have a histologically confirmed diagnosis of neuroblastmona with relapse in the CNS or LM.
    2. Patients need to have progressed in CNS/LM through induction therapy or have relapsed in CNS/LM following induction. CNS/LM progression/ relapse is defined as LM disease or metastatic deposits in the CNS parenchyma, (excluding skull bone-based metastases)
    3. Stable systemic disease not requiring chemo/ immunotherapy as judged by the investigator
    4. Ventriculoperitoneal (VP) shunts (only shunts with programmable valves can be accepted) is allowed however should be closed (or adjusted to highest pressure setting) during Investigational Medicinal Product (IMP) infusion. It is recommended that the VP shunt remains closed for approximately 5 hours after treatment and then readjusted. The shunt readjustment times are at the discretion of the treating physician. Closure of VP shunt is done at the discretion of the treating physician and the VP shunt should at any time based on patient safety evaluation be reopened at the assessment of the treating physician. Patients with ventriculo-atrial or ventriculo-pleural shunts are not eligible.
    5. Patients must be between the ages of birth and 18 years at the time of screening
    6. Patients must have a life expectancy of at least 3 months as judged by the investigator.
    7. Acceptable hematological status defined as:
    • Hemoglobin ≥8 g/dL
    • White blood cell count ≥1000/μL
    • Absolute neutrophil count ≥500/μL
    • Platelet count ≥50,000/μL
    8. Acceptable liver function defined as:
    • (ALT) and /or AST ≤ 5 times UNL
    • Bilirubin ≤3 x UNL
    In case either AST or ALT ≥3 x ULN, bilirubin must be ≤ 2 UNL
    9. Acceptable kidney function defined as:
    • eGFR >60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation (Appendix 3).
    10. Written informed consent from legal guardian(s) and/or child must be obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations
    E.4Principal exclusion criteria
    1. Patients with primary neuroblastoma (NB) in CNS
    2. Patients must not have obstructive or symptomatic communicating hydrocephalus.
    3. Patients must not have worsening of neurologic function, according to the assessment by investigator, within 3 weeks prior to first dose of 131I-omburtamab.
    4. Patients must not have an uncontrolled life-threatening infection.
    5. Patients must not have received cranial or spinal irradiation less than 3 weeks prior to first dose of 131I-omburtamab in this trial
    6. Patients must not have received systemic chemo/ immunotherapy (corticosteroids not included) less than 3 weeks prior to enrolment in this trial.
    7. Patients must not have received any B7-H3 treatment prior to enrolment in this trial.
    8. Patients must not have severe major non-hematologic organ toxicity; specifically, any renal, cardiac, hepatic, pulmonary, and gastrointestinal
    system toxicity must fall below Grade 3 prior to enrolment in this trial. Patients with stable neurological deficits (due to brain tumor) are not excluded. Patients with Grade 3 or lower hearing loss are not excluded.
    9. Patients must not be pregnant or breast-feeding
    10. Female patients of child-bearing potential (i.e. having experienced menarche) and male partners to female patients who do not agree to the use of effective contraception during treatment and for a period of 12 months after the last 131I-omburtamab dose. Effective contraception for women is defined as intrauterine devices or hormonal contraceptives(contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release). Effective contraception for male partners is defined as use of condoms. To be exempt from the requirement to use contraception after 131I-omburtamab treatment, one of the criteria described in section 9.2.11 of this protocol must be met.
    11. Fertile male patients who do not agree to the use of condoms during treatment and for a period of 12 months after the last 131I-omburtamab dose. For a sterilized male patient to be exempt from the requirement to use contraception after 131I-omburtamab treatment, he must have undergone surgical sterilization (vasectomy).
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival (OS) rate at 3 years after the first treatment dose of 131I-omburtamab
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 3 years after 131I-omburtamab treatment
    E.5.2Secondary end point(s)
    1. CNS/LM PFS at 6 and 12 months
    2. OS at 12 months
    3. ORR assessed as a combination of partial response and complete response as defined by the Response Assessment in Neuro-Oncology (RANO) group criteria for brain metastasis (Lin et al, 2015) or leptomeningeal metastases as defined by EANO-ESMO criteria (Le Rhun et al, 2017). ORR will be assessed at 6 months after the first treatment dose of 131Iomburtamab.
    4. ORR according to CSF cytology. Response is defined as a complete response when CSF converts from positive at baseline to negative after treatment
    with 131I-omburtamab.
    5. Whole-body, organ, blood, and CSF radiation dosimetry.
    6. Pharmacokinetic analysis of activity in blood and CSF including derivation of best-fit uptake and/or clearance parameters (half-times, maximum value) of time-activity concentration curves and of I-131 residence times (i.e., cumulated activity) concentrations (in μCi-h/g).
    7. The frequency, type, and duration of treatment-emergent severe adverse events and serious adverse events, including clinically significant laboratory abnormalities. All adverse events will be graded according to CTCAE, version 4.0.
    8. Performance assessment to monitor gross changes in neurological function is performed at week 26 and subsequently every 6 months during trial period.
    9. The rate of ADA occurrence assessed three weeks after the first and second treatment dose of 131I-omburtamab
    E.5.2.1Timepoint(s) of evaluation of this end point
    Short-term follow-up at 26 weeks after treatment and with long-term follow-up for up to 3 years following treatment
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    dosimetry
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    Spain
    Germany
    Denmark
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of trial (EOT) will occur when all patients have been followed until the visit at 3 years, or death whichever comes first.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 50
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) Yes
    F.1.1.3.1Number of subjects for this age range: 1
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 11
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 37
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 1
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients could be between the ages of birth and 18 years and therefore informed consent from legal guardian(s) and/or child must be obtained in accordance with local regulation. Pediatric patients must provide assent as required by local regulations
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 19
    F.4.2.2In the whole clinical trial 50
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Any treatment deemed safe and justified by the investigator can be administered according to clinical practice and at the discretion of the investigator
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-02-12
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-06-02
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 10 00:05:28 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA