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NeuroblastomaPhase 1MiniVanNCT02914405

Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma

A Phase 1 study testing Nivolumab and Ch14.18/CHO in people with Neuroblastoma, run by University Hospital Southampton NHS Foundation Trust at 3 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Neuroblastoma, the most common extra-cranial solid tumour in children, remains one of the major challenges in paediatric oncology. A promising way to further improve outcome in this disease appears to be the development of adjuvant therapeutic strategies. Read more about this study

Who is it for?
Ages 1 year to 99 yearsHealthy volunteers can take part
Conditions the study is for
Neuroblastoma
What is being tested?
Nivolumab and Ch14.18/CHO
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
3 sitesin 2 countries
Study dates
24 May 2018to 30 Sep 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 99 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • At study entry patients must be > 1 year
  • Relapsed or refractory high risk neuroblastoma (as defined by International Neuroblastoma Risk Group (INRG) criteria)
  • MIBG avid disease on imaging within 4 weeks to study entry.
  • ≥ 3 months since any myeloablative chemotherapy / stem cell rescue
  • ≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives since last dose of any monoclonal antibody therapy.
  • Patients must have a performance status greater or equal 60% (Lansky Score or Karnofsky)
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  • Estimated life expectancy ≥ 12 weeks
  • Adequate bone marrow function: Absolute Neutrophil Count (ANC) >1.0 x 10/L, platelets, 20 x 10/L and haemoglobin > 8.0 g/dL.
  • Adequate renal function: serum creatinine <1.5 mg/dL or a estimated creatinine clearance or radioisotope Glomerular Filtration Rate Study (GFR) of > 60 mL/minute/1.73m2.
  • Adequate cardiac function: shortening fraction of 28 % by echocardiogram.
  • Adequate hepatic function: Alanine transaminase (ALT) or Aspartate transaminase (AST) < 5 x ULN and a total bilirubin < 1.5 x Upper Limit of Normal (ULN)
  • Adequate lung function: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) >60% of the predicted by pulmonary function tests. Children unable to do Pulmonary Function Tests (PFTs) should have no dyspnea at rest and a pulse oximetry >94% on room air.
  • Adequate pancreatic function: serum lipase < 1.5 x upper limit normal
  • Patients may have had prior Central Nervous System (CNS) metastasis at point of entry to study, but patients with mIBG avid parenchymal brain lesions will be excluded. All CNS disease must be treated and stable prior for at least 4 weeks prior to starting trial 131-I mIBG therapy (see section 4). Patients with extra-axial disease (e.g. skull (bone) metastasis that do not invade the dura) may be enrolled providing there is no evidence of brain oedema.
  • Patients must consent to the placement of a central venous line, if one has not already been placed.
  • Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.
  • Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
  • Patients with seizure disorders may be enrolled if seizures are well controlled.
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional and national requirements for clinical trials must be met.
  • Expression of PD-L1 by tumour is not a pre-requisite
  • Parents or carers willing and able to comply with radiation safety measures needed for 131-I mIBG administration.
  • Patient must be judged capable of tolerating isolation procedures associated with 131-I-mIBG therapy

Who cannot join

  • Patients who have previously received ch14.18 (CHO or SP2/0) will not be excluded unless they have had severe or life threatening toxicity necessitating withdrawal of treatment previously or if they have a strong/neutralizing Human Antichimeric Antibody (HACA) (≥ 10 μg/ml)
  • Patients who have had previous 131-I mIBG therapy will not be excluded
  • Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study
  • Previous allogeneic stem cell transplant or solid organ transplant
  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients receiving systemic corticosteroids (other than physiological replacement) or other immunosuppressive agents within 14 days prior to study entry
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  • Unable to maintain platelets ≥ 50 x 109/l without transfusion
  • HIV or Hepatitis B or C infection
  • Patients with significant intercurrent illnesses and/or any of the following:
  • 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.
  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United Kingdom2 sites

  • University College London Hospital

    London, London, NW1 2BU

  • University Hospital Southampton NHS Foundation Trust

    Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

United States1 site

  • University of Wisconsin Carbone Cancer Center; UW Hospital and Clinics; American Family Children's Hospital

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: A Phase I Study of 131-1 mIBG Followed by Nivolumab and Dinutuximab Beta in Children With Relapsed/Refractory Neuroblastoma

Neuroblastoma, the most common extra-cranial solid tumour in children, remains one of the major challenges in paediatric oncology. A promising way to further improve outcome in this disease appears to be the development of adjuvant therapeutic strategies. In this research the anti-GD2 antibody, which is a standard treatment, is to be combined with 131-l Metaiodobenzylguanidine (mlBG) and anti-Programmed Cell Death Protein 1 (anti-PD1) antibody Nivolumab - the investigated drugs - with the aim of generating sustained anti-neuroblastoma immunity. In particular it will be determined the safety and tolerability of the novel combination as well as documented any evidence of efficacy in paediatric patients with relapsed and refractory high risk neuroblastoma.

This study is sponsored by the University Hospital Southampton and will take place in 4 hospitals in the United Kingdom, Germany and USA. The estimated duration of the study is 2 years, starting in December 2016.

Read more

This is an "adaptive study". Such design uses accumulating of data from the ongoing trial to modify aspects of the study (e.g. duration, number of treatments) without undermining its validity or integrity. There will be 3 cohorts of patients. As safety of Nivolumab is well established, Cohort 1 will assess its safety and tolerability in combination with 131-l mlBG. Cohort 2 will then add anti-GD2 to the drug combination, assessing safety and tolerability. Cohort 3 will escalate all 3 agents to the full 100% dose level to assure safety for expanded analyses of clinical and laboratory data at that dose level.

Patients will initially be recruited into Cohort 1. Patients must have completed at least 12 weeks of trial treatment without reaching a Dose Limiting Toxicity before a patient can be recruited to the next cohort.

A minimum of 3 evaluable patients will be treated in cohorts 1-3. Assuming the full dose combination therapy (cohort) is tolerable, 15 evaluable patients will be treated.

Conditions
Neuroblastoma
Being tested
Nivolumab, Ch14.18/CHO
Keywords
131-I-mIBG therapy, ch14.18/CHO, Nivolumab, MiniVan
Medical subject headings
Neuroblastoma

What participants receive

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

  • NivolumabDrug

    Also called BMS-936558, MDX1106, ONO-4538, anti-PD-1) NSC#748726

    Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains consisting of 440 amino acids and 2 identical light chains. Molecular weight is 146,221 daltons.

  • Ch14.18/CHODrug

    Also called Mouse-human chimeric monoclonal anti-GD2 Immunoglobulin G1 (IgG1) antibody

    APN311 (ch14.18/CHO) is manufactured in a Good Manufacturing Practice (GMP) compliant facility of Polymun Scientific, Austria according to a state of the art aseptic manufacturing process based on a characterized and stable Chinese Hamster Ovary (CHO) cell line. After propagation of the working cell bank (WCB) in small volume vessels/bioreactors, manufacture is carried out in a 2500 L stirred tank reactor utilizing components which are free of material of animal or human origin.

Study groups in NCT02914405
Study groupRoleWhat they receive
TreatmentExperimentalThe dose and schedule of 131-I mIBG will be constant, and the doses of ch14.18/ CHO and Nivolumab determined by cohort: * Cohort I: 3 mg/kg Nivolumab (100% adult dose). No ch14.18/CHO. (3-6 patients) * Cohort II: 50mg/m2/cycle ch14.18/CHO (50% established Long Term Intervention (LTI) dose) and 3 mg/kg Nivolumab (100% adult dose) (3-6 patients) * Cohort III: 100mg/m2/cycle ch14.18/CHO (100% established LTI dose) and 3 mg/kg Nivolumab (100% adult dose) (initial 3-6 patients, expanded to 15 patient cohort if tolerated)
Receives: Drug: Nivolumab; Drug: Ch14.18/CHO

What is being measured

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

  1. Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients

    • To determine the safety and tolerability of the novel combination of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients, assessed by nature, frequency, severity and timing of adverse events, including serious adverse events and immune related adverse events during administration of ch14.18/CHO

    Measured: 2 Years

Secondary outcomes (3)

  1. Anti-tumour response in patients with measureable disease as measured by immunocytology, MIBG, CT and/or MRI in patients receiving 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma

    To document any evidence of efficacy of 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma (time to progression)

    Measured: 2 Years

  2. Anti-tumour response in patients with measureable disease as measured by immunocytology, MIBG, CT and/or MRI in patients receiving 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma

    To document any evidence of efficacy of 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma (objective response rate)

    Measured: 2 Years

  3. KIR/KIR-Ligand genotype, FcγR genotype

    To provide descriptive analysis of any associations between KIR/KIR-Ligand genotype, FcγR genotype and response

    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 posted26 Sep 2016 (estimated)
  2. Study start24 May 2018
  3. Primary completion30 Jun 2025
  4. Study completion30 Sep 2026 (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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02914405
Sponsor's protocol ID
RHM CHI0811
Other IDs
2016-002221-11, 2016
Acronym
MiniVan
Status last verified
Apr 2026
First submitted
25 Aug 2016
Last updated
28 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Garra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, Thode HC Jr. Validation of the Wong-Baker FACES Pain Rating Scale in pediatric emergency department patients. Acad Emerg Med. 2010 Jan;17(1):50-4. doi: 10.1111/j.1553-2712.2009.00620.x. Epub 2009 Dec 9.

    PubMed 20003121

  • Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain. 2001 Aug;93(2):173-183. doi: 10.1016/S0304-3959(01)00314-1.

    PubMed 11427329

  • Bulloch B, Tenenbein M. Validation of 2 pain scales for use in the pediatric emergency department. Pediatrics. 2002 Sep;110(3):e33. doi: 10.1542/peds.110.3.e33.

    PubMed 12205283

  • Wilson GA, Doyle E. Validation of three paediatric pain scores for use by parents. Anaesthesia. 1996 Nov;51(11):1005-7. doi: 10.1111/j.1365-2044.1996.tb14991.x.

    PubMed 8943588

  • Buttner W, Breitkopf L, Miele B, Finke W. [Initial results of the reliability and validity of a German-language scale for the quantitative measurement of postoperative pain in young children]. Anaesthesist. 1990 Nov;39(11):593-602. German.

    PubMed 2288408

  • Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974 Jun 22;2(5920):656-9. doi: 10.1136/bmj.2.5920.656.

    PubMed 4835444

  • Matthay KK, Yanik G, Messina J, Quach A, Huberty J, Cheng SC, Veatch J, Goldsby R, Brophy P, Kersun LS, Hawkins RA, Maris JM. Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma. J Clin Oncol. 2007 Mar 20;25(9):1054-60. doi: 10.1200/JCO.2006.09.3484.

    PubMed 17369569

  • Matthay KK, Quach A, Huberty J, Franc BL, Hawkins RA, Jackson H, Groshen S, Shusterman S, Yanik G, Veatch J, Brophy P, Villablanca JG, Maris JM. Iodine-131--metaiodobenzylguanidine double infusion with autologous stem-cell rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I study. J Clin Oncol. 2009 Mar 1;27(7):1020-5. doi: 10.1200/JCO.2007.15.7628. Epub 2009 Jan 26.

    PubMed 19171714

  • Matthay KK, Weiss B, Villablanca JG, Maris JM, Yanik GA, Dubois SG, Stubbs J, Groshen S, Tsao-Wei D, Hawkins R, Jackson H, Goodarzian F, Daldrup-Link H, Panigrahy A, Towbin A, Shimada H, Barrett J, Lafrance N, Babich J. Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. J Nucl Med. 2012 Jul;53(7):1155-63. doi: 10.2967/jnumed.111.098624. Epub 2012 Jun 14.

    PubMed 22700000

  • Wilson JS, Gains JE, Moroz V, Wheatley K, Gaze MN. A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. Eur J Cancer. 2014 Mar;50(4):801-15. doi: 10.1016/j.ejca.2013.11.016. Epub 2013 Dec 12.

    PubMed 24333097

  • Gaze MN, Chang YC, Flux GD, Mairs RJ, Saran FH, Meller ST. Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma. Cancer Biother Radiopharm. 2005 Apr;20(2):195-9. doi: 10.1089/cbr.2005.20.195.

    PubMed 15869455

  • Suzuki M, Cheung NK. Disialoganglioside GD2 as a therapeutic target for human diseases. Expert Opin Ther Targets. 2015 Mar;19(3):349-62. doi: 10.1517/14728222.2014.986459. Epub 2015 Jan 20.

    PubMed 25604432

  • Honsik CJ, Jung G, Reisfeld RA. Lymphokine-activated killer cells targeted by monoclonal antibodies to the disialogangliosides GD2 and GD3 specifically lyse human tumor cells of neuroectodermal origin. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7893-7. doi: 10.1073/pnas.83.20.7893.

    PubMed 3094017

  • Gillies SD, Lo KM, Wesolowski J. High-level expression of chimeric antibodies using adapted cDNA variable region cassettes. J Immunol Methods. 1989 Dec 20;125(1-2):191-202. doi: 10.1016/0022-1759(89)90093-8.

    PubMed 2514231

  • Zeng Y, Fest S, Kunert R, Katinger H, Pistoia V, Michon J, Lewis G, Ladenstein R, Lode HN. Anti-neuroblastoma effect of ch14.18 antibody produced in CHO cells is mediated by NK-cells in mice. Mol Immunol. 2005 Jul;42(11):1311-9. doi: 10.1016/j.molimm.2004.12.018. Epub 2005 Apr 7.

    PubMed 15950727

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab and Ch14.18/CHO in people with Neuroblastoma, run by University Hospital Southampton NHS Foundation Trust at 3 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 23 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 28 Apr 2026. 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 United Kingdom, United States. 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?

This study is still under way. Results are not available in the source record yet.

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?

Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients (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 NCT02914405, which also lists 51 linked publications.

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 28 Apr 2026.

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