Ignite Creation Date:
2025-12-25 @ 1:12 AM
Ignite Modification Date:
2026-02-26 @ 8:12 PM
Study NCT ID:
NCT02173093
Status:
UNKNOWN
Last Update Posted:
2019-01-29
First Post:
2014-06-22
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'submissionInfos': [{'resetDate': '2022-03-25', 'releaseDate': '2022-02-28'}, {'resetDate': '2025-09-18', 'releaseDate': '2025-08-28'}, {'resetDate': '2025-11-17', 'releaseDate': '2025-11-04'}], 'estimatedResultsFirstSubmitDate': '2022-02-28'}}, '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': 'D007376', 'term': 'Interleukin-2'}, {'id': 'C082598', 'term': 'aldesleukin'}, {'id': 'D016178', 'term': 'Granulocyte-Macrophage Colony-Stimulating Factor'}, {'id': 'C081222', 'term': 'sargramostim'}], 'ancestors': [{'id': 'D007378', 'term': 'Interleukins'}, {'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D008222', 'term': 'Lymphokines'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D003115', 'term': 'Colony-Stimulating Factors'}, {'id': 'D006023', 'term': 'Glycoproteins'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D016298', 'term': 'Hematopoietic Cell Growth Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2014-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-01', 'completionDateStruct': {'date': '2019-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-01-25', 'studyFirstSubmitDate': '2014-06-22', 'studyFirstSubmitQcDate': '2014-06-23', 'lastUpdatePostDateStruct': {'date': '2019-01-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-06-24', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2019-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum tolerated dose (MTD) of GD2Bi-aATC', 'timeFrame': '35 days', 'description': 'Safety of GD2Bi-aATC infusions is evaluated to determine MTD'}], 'secondaryOutcomes': [{'measure': 'Anti-tumor activity', 'timeFrame': 'Up to 12 months', 'description': 'Objective response rate to GD2Bi-aATC infusions'}, {'measure': 'Immune responses after GD2Bi-aATC infusions', 'timeFrame': 'Up to 12 months', 'description': "In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes"}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Neuroblastoma', 'Solid tumor', 'Immunotherapy targeting GD2', 'Bispecific antibodies', 'Activated T cells'], 'conditions': ['Disseminated Neuroblastoma', 'Recurrent Neuroblastoma']}, 'referencesModule': {'references': [{'pmid': '33986124', 'type': 'DERIVED', 'citation': 'Park JA, Santich BH, Xu H, Lum LG, Cheung NV. Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release. J Immunother Cancer. 2021 May;9(5):e002222. doi: 10.1136/jitc-2020-002222.'}]}, 'descriptionModule': {'briefSummary': 'Previous research has demonstrated that investigators can coat (arm) T cells with a special molecule called GD2 bispecific antibody that will help T cells recognize neuroblastoma and osteosarcoma cells and kill them. This bispecific antibody recognizes GD2, a protein found on almost all neuroblastoma and osteosarcoma cells. The investigators put the GD2 bispecific antibody on T cells and give large numbers of these T cells back to patients. The investigators think that these T cells may have a better chance of killing GD2 expressing tumor cells when they are armed with GD2 bispecific antibody. This trial studies the side effects and best dose of activated T cells armed with GD2 bispecific antibody and how well they work in treating patients with neuroblastoma, osteosarcoma, and other GD2-positive solid tumors.', 'detailedDescription': 'PRIMARY OBJECTIVES:\n\nI. To perform a phase I dose-escalation study in patients with recurrent or refractory neuroblastoma (NB) and other GD2-positive tumors to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) for anti-CD3 x hu3F8 bispecific antibody (GD2Bi)-armed activated T cells (aATC) infused twice a week for a total of eight infusions in combination with daily IL-2 (300,000 IU/m\\^2/day) and GM-CSF (250 ug/m\\^2 twice per week) in a standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10\\^6 cells/kg/infusion dose levels.\n\nII. To conduct a phase II clinical trial to explore efficacy and confirm the toxicity profile of GD2Bi-aATC combined with IL-2 and GM-CSF in a phase II expansion cohort of 22 patients with neuroblastoma (NB) using MTD determined in the phase I.\n\nSECONDARY OBJECTIVES:\n\nI. Evaluate immune responses in the phase I/II trial by sequential monitoring of anti-NB cytotoxicity of peripheral blood lymphocytes and IFN-gamma EliSpots directed at NB lines.\n\nII. To evaluate persistence of aATC in the blood and tumor biopsies by staining for murine IgG2a to confirm trafficking of armed T cells to tumor.\n\nIII. To conduct exploratory study of (18F FDG) positron emission tomography (PET)/computed tomography (CT) after armed ATC infusions in selected patients with PET/CT measurable soft tissue and skeletal lesions.\n\nOUTLINE: This is a phase I, dose-escalation study of OKT3/humanized 3F8 bispecific antibody-aATC followed by a phase II study.\n\nPatients receive IL-2 subcutaneously (SC) daily on days -2 to 35, sargramostim SC twice weekly for 4 weeks, and OKT3/humanized 3F8 bispecific antibody-aATC intravenously (IV) over 30 minutes twice weekly for 4 weeks.\n\nAfter completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '29 Years', 'minimumAge': '13 Months', 'healthyVolunteers': False, 'eligibilityCriteria': "The study is now in the phase II expansion phase.\n\nInclusion Criteria for phase II:\n\n* The target tumor is limited to neuroblastoma and the diagnosis should be histologically verified.\n* Patients must have refractory or recurrent malignancy; patient's current disease state must be one for which no known curative therapy is available;\n* Patients should not receive any other experimental or phase 1 therapy within 3 weeks prior to study enrollment and monoclonal antibody therapy within 6 weeks\n* To be eligible for phase I study patients should have primary refractory or relapsed disease as evidenced by:\n\n * Local tumor recurrence measurable on CT or magnetic resonance imaging (MRI) scans with or without metastatic lesions\n * Refractory bone marrow involvement in patients with NB\n * NB with MIBG-positive skeletal lesions\n* The presence of radiographically measurable disease immediately prior to start of Phase I immunotherapy is not an eligibility requirement in the following situations:\n\n * In patients with NB who have documented bone marrow (BM) involvement;\n * In patients with NB who have MIBG-positive bony lesion(s);\n* An additional eligibility requirement for phase II study includes the presence of radiographically measurable disease with the exception of MIBG-positive NB or NB with bone marrow involvement:\n* Patients must have a Lansky or Karnofsky performance status score of \\>= 70\n* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy\n\n * Myelosuppressive chemotherapy: must not have received within 3 weeks of starting immunotherapy (IT)\n * Hematopoietic growth factors: at least 7 days since the last dose of growth factor therapy\n * Immunotherapy: at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody\n* Normal organ function\n* All patients or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines\n* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met\n\nExclusion Criteria:\n\n* Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are postmenarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 3 months after the last dose of GD2Bi-aATC; breastfeeding women should be excluded\n* Patients who have an uncontrolled infection are not eligible\n* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible"}, 'identificationModule': {'nctId': 'NCT02173093', 'briefTitle': 'Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma', 'organization': {'class': 'OTHER', 'fullName': 'University of Virginia'}, 'officialTitle': 'Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study', 'orgStudyIdInfo': {'id': '19031'}, 'secondaryIdInfos': [{'id': 'NCI-2014-01149', 'type': 'REGISTRY', 'domain': 'CTRP (Clinical Trial Reporting Program)'}, {'id': '2013-171', 'type': 'OTHER', 'domain': 'Barbara Ann Karmanos Cancer Institute'}, {'id': 'P30CA022453', 'link': 'https://reporter.nih.gov/quickSearch/P30CA022453', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (IL-2, GM-CSF, GD2Bi-aATC)', 'description': 'Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.', 'interventionNames': ['Biological: IL-2', 'Biological: GD2Bi-aATC', 'Biological: GM-CSF', 'Other: laboratory evaluations of immune responses']}], 'interventions': [{'name': 'IL-2', 'type': 'BIOLOGICAL', 'otherNames': ['aldesleukin', 'Proleukin', 'recombinant human interleukin-2', 'recombinant interleukin-2'], 'description': 'Given SC', 'armGroupLabels': ['Treatment (IL-2, GM-CSF, GD2Bi-aATC)']}, {'name': 'GD2Bi-aATC', 'type': 'BIOLOGICAL', 'otherNames': ['GD2Bi-armed aATC'], 'description': 'Given IV', 'armGroupLabels': ['Treatment (IL-2, GM-CSF, GD2Bi-aATC)']}, {'name': 'GM-CSF', 'type': 'BIOLOGICAL', 'otherNames': ['sargramostin', 'Leukine', 'Prokine'], 'description': 'Given SC', 'armGroupLabels': ['Treatment (IL-2, GM-CSF, GD2Bi-aATC)']}, {'name': 'laboratory evaluations of immune responses', 'type': 'OTHER', 'otherNames': ['laboratory biomarker analysis'], 'description': 'Correlative studies', 'armGroupLabels': ['Treatment (IL-2, GM-CSF, GD2Bi-aATC)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '48201', 'city': 'Detroit', 'state': 'Michigan', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Maxim Y. Yankelevich, MD', 'role': 'CONTACT', 'email': 'myankele@med.wayne.edu', 'phone': '313-745-5516'}, {'name': 'Diana Gomez, MPH', 'role': 'CONTACT', 'phone': '313-745-7163'}, {'name': 'Maxim Y. Yankelevich, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': "Children's Hospital of Michigan", 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Shakeel Modak, M.D.', 'role': 'CONTACT', 'email': 'modaks@mskcc.org'}, {'name': 'Shakeel Modak, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Alexandar Chou, M.D.', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Memorial Sloan-Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '22908', 'city': 'Charlottesville', 'state': 'Virginia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Daniel (Trey) Lee, MD', 'role': 'CONTACT', 'email': 'DWL4Q@Virginia.edu', 'phone': '434-297-4289'}, {'name': 'Daniel (Trey) Lee, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Virginia, Department of Pediatrics, Hematology/Oncology', 'geoPoint': {'lat': 38.02931, 'lon': -78.47668}}], 'centralContacts': [{'name': 'Holly Davis', 'role': 'CONTACT', 'email': 'haw5d@virginia.edu'}], 'overallOfficials': [{'name': 'Maxim Yankelevich', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Barbara Ann Karmanos Cancer Institute'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Virginia', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Daniel W. Lee, MD', 'investigatorAffiliation': 'University of Virginia'}}}, 'annotationSection': {'annotationModule': {'unpostedAnnotation': {'unpostedEvents': [{'date': '2022-02-28', 'type': 'RELEASE'}, {'date': '2022-03-25', 'type': 'RESET'}, {'date': '2025-08-28', 'type': 'RELEASE'}, {'date': '2025-09-18', 'type': 'RESET'}, {'date': '2025-11-04', 'type': 'RELEASE'}, {'date': '2025-11-17', 'type': 'RESET'}], 'unpostedResponsibleParty': 'Lawrence Lum, MD, Professor of Medicine, University of Virginia'}}}}