Ignite Creation Date:
2025-12-25 @ 3:30 AM
Ignite Modification Date:
2026-01-11 @ 1:06 PM
Study NCT ID:
NCT02914405
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-22
First Post:
2016-08-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009447', 'term': 'Neuroblastoma'}], 'ancestors': [{'id': 'D018241', 'term': 'Neuroectodermal Tumors, Primitive, Peripheral'}, {'id': 'D018242', 'term': 'Neuroectodermal Tumors, Primitive'}, {'id': 'D018302', 'term': 'Neoplasms, Neuroepithelial'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077594', 'term': 'Nivolumab'}, {'id': 'D007074', 'term': 'Immunoglobulin G'}, {'id': 'D000906', 'term': 'Antibodies'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D007132', 'term': 'Immunoglobulin Isotypes'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 44}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2018-05-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-12', 'completionDateStruct': {'date': '2025-11-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-10-20', 'studyFirstSubmitDate': '2016-08-25', 'studyFirstSubmitQcDate': '2016-09-22', 'lastUpdatePostDateStruct': {'date': '2025-10-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-09-26', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2025-06-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients', 'timeFrame': '2 Years', 'description': '• 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'}], 'secondaryOutcomes': [{'measure': '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', 'timeFrame': '2 Years', 'description': '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)'}, {'measure': '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', 'timeFrame': '2 Years', 'description': '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)'}, {'measure': 'KIR/KIR-Ligand genotype, FcγR genotype', 'timeFrame': '2 Years', 'description': 'To provide descriptive analysis of any associations between KIR/KIR-Ligand genotype, FcγR genotype and response'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['131-I-mIBG therapy', 'ch14.18/CHO', 'Nivolumab', 'MiniVan'], 'conditions': ['Neuroblastoma']}, 'referencesModule': {'references': [{'pmid': '20003121', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '11427329', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '12205283', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '8943588', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '2288408', 'type': 'BACKGROUND', 'citation': 'Buttner W, Breitkopf L, Miele B, Finke W. 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J Nucl Med. 2012 Jul;53(7):1155-63. doi: 10.2967/jnumed.111.098624. Epub 2012 Jun 14.'}, {'pmid': '24333097', 'type': 'RESULT', 'citation': '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.'}, {'pmid': '15869455', 'type': 'RESULT', 'citation': '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.'}, {'pmid': '25604432', 'type': 'RESULT', 'citation': '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. 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Epub 2005 Apr 7.'}, {'pmid': '20879881', 'type': 'RESULT', 'citation': "Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123."}, {'pmid': '21798350', 'type': 'RESULT', 'citation': 'Ora I, Eggert A. Progress in treatment and risk stratification of neuroblastoma: impact on future clinical and basic research. Semin Cancer Biol. 2011 Oct;21(4):217-28. doi: 10.1016/j.semcancer.2011.07.002. Epub 2011 Jul 20.'}, {'pmid': '1638557', 'type': 'RESULT', 'citation': 'Handgretinger R, Baader P, Dopfer R, Klingebiel T, Reuland P, Treuner J, Reisfeld RA, Niethammer D. A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. 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Phase I trial of the chimeric anti-GD2 monoclonal antibody ch14.18 in patients with malignant melanoma. Hum Antibodies Hybridomas. 1992 Jan;3(1):19-24.'}, {'pmid': '7718335', 'type': 'RESULT', 'citation': 'Handgretinger R, Anderson K, Lang P, Dopfer R, Klingebiel T, Schrappe M, Reuland P, Gillies SD, Reisfeld RA, Neithammer D. A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer. 1995;31A(2):261-7. doi: 10.1016/0959-8049(94)00413-y.'}, {'pmid': '9626218', 'type': 'RESULT', 'citation': 'Yu AL, Uttenreuther-Fischer MM, Huang CS, Tsui CC, Gillies SD, Reisfeld RA, Kung FH. Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol. 1998 Jun;16(6):2169-80. doi: 10.1200/JCO.1998.16.6.2169.'}, {'pmid': '21298742', 'type': 'RESULT', 'citation': 'Simon T, Berthold F, Borkhardt A, Kremens B, De Carolis B, Hero B. 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Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012 Feb 15;72(4):917-27. doi: 10.1158/0008-5472.CAN-11-1620. Epub 2011 Dec 20.'}, {'pmid': '24848257', 'type': 'RESULT', 'citation': 'Highfill SL, Cui Y, Giles AJ, Smith JP, Zhang H, Morse E, Kaplan RN, Mackall CL. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci Transl Med. 2014 May 21;6(237):237ra67. doi: 10.1126/scitranslmed.3007974.'}, {'pmid': '20570856', 'type': 'RESULT', 'citation': 'Zhou Q, Munger ME, Highfill SL, Tolar J, Weigel BJ, Riddle M, Sharpe AH, Vallera DA, Azuma M, Levine BL, June CH, Murphy WJ, Munn DH, Blazar BR. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 2010 Oct 7;116(14):2484-93. doi: 10.1182/blood-2010-03-275446. Epub 2010 Jun 22.'}, {'pmid': '22658128', 'type': 'RESULT', 'citation': 'Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.'}, {'pmid': '22658127', 'type': 'RESULT', 'citation': 'Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.'}, {'pmid': '23724867', 'type': 'RESULT', 'citation': 'Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122-33. doi: 10.1056/NEJMoa1302369. Epub 2013 Jun 2.'}, {'pmid': '15269160', 'type': 'RESULT', 'citation': 'Neal ZC, Yang JC, Rakhmilevich AL, Buhtoiarov IN, Lum HE, Imboden M, Hank JA, Lode HN, Reisfeld RA, Gillies SD, Sondel PM. Enhanced activity of hu14.18-IL2 immunocytokine against murine NXS2 neuroblastoma when combined with interleukin 2 therapy. Clin Cancer Res. 2004 Jul 15;10(14):4839-47. doi: 10.1158/1078-0432.CCR-03-0799.'}, {'pmid': '9362156', 'type': 'RESULT', 'citation': 'Lode HN, Xiang R, Varki NM, Dolman CS, Gillies SD, Reisfeld RA. Targeted interleukin-2 therapy for spontaneous neuroblastoma metastases to bone marrow. J Natl Cancer Inst. 1997 Nov 5;89(21):1586-94. doi: 10.1093/jnci/89.21.1586.'}, {'pmid': '19638464', 'type': 'RESULT', 'citation': 'Johnson EE, Yamane BH, Buhtoiarov IN, Lum HD, Rakhmilevich AL, Mahvi DM, Gillies SD, Sondel PM. Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma. Clin Cancer Res. 2009 Aug 1;15(15):4875-84. doi: 10.1158/1078-0432.CCR-09-0110. Epub 2009 Jul 28.'}, {'pmid': '22844125', 'type': 'RESULT', 'citation': 'Yang RK, Kalogriopoulos NA, Rakhmilevich AL, Ranheim EA, Seo S, Kim K, Alderson KL, Gan J, Reisfeld RA, Gillies SD, Hank JA, Sondel PM. Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retention. J Immunol. 2012 Sep 1;189(5):2656-64. doi: 10.4049/jimmunol.1200934. Epub 2012 Jul 27.'}, {'pmid': '23661160', 'type': 'RESULT', 'citation': 'Yang RK, Kalogriopoulos NA, Rakhmilevich AL, Ranheim EA, Seo S, Kim K, Alderson KL, Gan J, Reisfeld RA, Gillies SD, Hank JA, Sondel PM. Intratumoral treatment of smaller mouse neuroblastoma tumors with a recombinant protein consisting of IL-2 linked to the hu14.18 antibody increases intratumoral CD8+ T and NK cells and improves survival. Cancer Immunol Immunother. 2013 Aug;62(8):1303-13. doi: 10.1007/s00262-013-1430-x. Epub 2013 May 10.'}, {'pmid': '23649004', 'type': 'RESULT', 'citation': 'Williams EL, Dunn SN, James S, Johnson PW, Cragg MS, Glennie MJ, Gray JC. Immunomodulatory monoclonal antibodies combined with peptide vaccination provide potent immunotherapy in an aggressive murine neuroblastoma model. Clin Cancer Res. 2013 Jul 1;19(13):3545-55. doi: 10.1158/1078-0432.CCR-12-3226. Epub 2013 May 6.'}, {'pmid': '19626208', 'type': 'RESULT', 'citation': 'Zernikow B, Hechler T. Pain therapy in children and adolescents. Dtsch Arztebl Int. 2008 Jul;105(28-29):511-21; quiz 521-2. doi: 10.3238/arztebl.2008.0511. Epub 2008 Jul 14.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nThis 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.\n\nThis 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.\n\nPatients 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.\n\nA 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '1 Year', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* At study entry patients must be \\> 1 year\n* Relapsed or refractory high risk neuroblastoma (as defined by International Neuroblastoma Risk Group (INRG) criteria)\n* MIBG avid disease on imaging within 4 weeks to study entry.\n* ≥ 3 months since any myeloablative chemotherapy / stem cell rescue\n* ≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives since last dose of any monoclonal antibody therapy.\n* Patients must have a performance status greater or equal 60% (Lansky Score or Karnofsky)\n* Estimated life expectancy ≥ 12 weeks\n* Adequate bone marrow function: Absolute Neutrophil Count (ANC) \\>1.0 x 10/L, platelets, 20 x 10/L and haemoglobin \\> 8.0 g/dL.\n* 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.\n* Adequate cardiac function: shortening fraction of 28 % by echocardiogram.\n* 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)\n* 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.\n* Adequate pancreatic function: serum lipase \\< 1.5 x upper limit normal\n* 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.\n* Patients must consent to the placement of a central venous line, if one has not already been placed.\n* Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.\n* 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.\n* Patients with seizure disorders may be enrolled if seizures are well controlled.\n* All patients and/or their parents or legal guardians must sign a written informed consent\n* All institutional and national requirements for clinical trials must be met.\n* Expression of PD-L1 by tumour is not a pre-requisite\n* Parents or carers willing and able to comply with radiation safety measures needed for 131-I mIBG administration.\n* Patient must be judged capable of tolerating isolation procedures associated with 131-I-mIBG therapy\n\nExclusion Criteria\n\n* 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)\n* Patients who have had previous 131-I mIBG therapy will not be excluded\n* Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study\n* Previous allogeneic stem cell transplant or solid organ transplant\n* 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\n* Patients receiving systemic corticosteroids (other than physiological replacement) or other immunosuppressive agents within 14 days prior to study entry\n* Unable to maintain platelets ≥ 50 x 109/l without transfusion\n* HIV or Hepatitis B or C infection\n* Patients with significant intercurrent illnesses and/or any of the following:\n\n * Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.\n * Patients with significant psychiatric disabilities or uncontrolled seizure disorders.\n * Patients with active infections.\n * Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade \\>2) are ineligible.\n * Patients with clinically significant, symptomatic, pleural effusions.\n * Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs.'}, 'identificationModule': {'nctId': 'NCT02914405', 'acronym': 'MiniVan', 'briefTitle': 'Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital Southampton NHS Foundation Trust'}, 'officialTitle': 'A Phase I Study of 131-1 mIBG Followed by Nivolumab and Dinutuximab Beta in Children With Relapsed/Refractory Neuroblastoma', 'orgStudyIdInfo': {'id': 'RHM CHI0811'}, 'secondaryIdInfos': [{'id': '2016-002221-11', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment', 'description': 'The dose and schedule of 131-I mIBG will be constant, and the doses of ch14.18/ CHO and Nivolumab determined by cohort:\n\n* Cohort I: 3 mg/kg Nivolumab (100% adult dose). No ch14.18/CHO. (3-6 patients)\n* 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)\n* 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)', 'interventionNames': ['Drug: Nivolumab', 'Drug: Ch14.18/CHO']}], 'interventions': [{'name': 'Nivolumab', 'type': 'DRUG', 'otherNames': ['BMS-936558', 'MDX1106', 'ONO-4538', 'anti-PD-1) NSC#748726', 'IND #124729'], 'description': '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.', 'armGroupLabels': ['Treatment']}, {'name': 'Ch14.18/CHO', 'type': 'DRUG', 'otherNames': ['Mouse-human chimeric monoclonal anti-GD2 Immunoglobulin G1 (IgG1) antibody'], 'description': '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.', 'armGroupLabels': ['Treatment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '53792', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': "University of Wisconsin Carbone Cancer Center; UW Hospital and Clinics; American Family Children's Hospital", 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}, {'zip': 'SO16 6YD', 'city': 'Southampton', 'state': 'Hampshire', 'country': 'United Kingdom', 'facility': 'University Hospital Southampton NHS Foundation Trust', 'geoPoint': {'lat': 50.90395, 'lon': -1.40428}}, {'zip': 'NW1 2BU', 'city': 'London', 'state': 'London', 'country': 'United Kingdom', 'facility': 'University College London Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Juliet Gray', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Consultant Paediatric Oncologist'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital Southampton NHS Foundation Trust', 'class': 'OTHER'}, 'collaborators': [{'name': 'University College London Hospitals', 'class': 'OTHER'}, {'name': 'University of Wisconsin, Madison', 'class': 'OTHER'}, {'name': 'University Hospital Greifswald', 'class': 'OTHER'}, {'name': "Solving Kids' Cancer US/EU", 'class': 'UNKNOWN'}, {'name': 'Joining Against Cancer in Kids', 'class': 'UNKNOWN'}, {'name': 'The Band of Parents', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}