Ignite Creation Date:
2025-12-25 @ 12:13 AM
Ignite Modification Date:
2026-04-13 @ 11:08 AM
Study NCT ID:
NCT01758458
Status:
TERMINATED
Last Update Posted:
2017-04-19
First Post:
2012-12-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015266', 'term': 'Carcinoma, Merkel Cell'}], 'ancestors': [{'id': 'D027601', 'term': 'Polyomavirus Infections'}, {'id': 'D004266', 'term': 'DNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014412', 'term': 'Tumor Virus Infections'}, {'id': 'D018278', 'term': 'Carcinoma, Neuroendocrine'}, {'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'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': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C082598', 'term': 'aldesleukin'}, {'id': 'D011878', 'term': 'Radiotherapy'}, {'id': 'D011827', 'term': 'Radiation'}, {'id': 'D016899', 'term': 'Interferon-beta'}], 'ancestors': [{'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D055585', 'term': 'Physical Phenomena'}, {'id': 'D007370', 'term': 'Interferon Type I'}, {'id': 'D007372', 'term': 'Interferons'}, {'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': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 4}}, 'statusModule': {'whyStopped': 'A Phase I/II study (NCT01758458) is now recruiting', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2013-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-04', 'dispFirstSubmitDate': '2017-03-03', 'completionDateStruct': {'date': '2016-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-04-17', 'studyFirstSubmitDate': '2012-12-27', 'dispFirstSubmitQcDate': '2017-03-03', 'studyFirstSubmitQcDate': '2012-12-27', 'dispFirstPostDateStruct': {'date': '2017-03-07', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2017-04-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-01-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Evidence and nature of toxicity related to the study treatment assessed using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0', 'timeFrame': 'Up to 4 weeks', 'description': 'The treatment will be considered to have an acceptable safety profile if the observed toxicity rate is consistent with a true rate that does not exceed 30%.'}, {'measure': 'Evidence of response based on "median time to new metastasis"', 'timeFrame': 'Up to 4 years', 'description': 'Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.'}], 'secondaryOutcomes': [{'measure': 'Disease response by RECIST criteria', 'timeFrame': 'Up to 4 years'}, {'measure': 'Functional capacity of transferred T cells', 'timeFrame': 'Up to 4 years'}, {'measure': 'MCC-specific survival', 'timeFrame': 'Up to 4 years'}, {'measure': 'Persistence of transferred T cells in blood and in tumor', 'timeFrame': 'Up to 4 years'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Recurrent Merkel Cell Carcinoma', 'Stage IV Merkel Cell Carcinoma']}, 'descriptionModule': {'briefSummary': 'This phase I/II trial studies the side effects and best way to give laboratory treated autologous T cells together with aldesleukin and to see how well it works in treating patients with merkel cell carcinoma that has spread from the primary site (place where it started) to other places in the body. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate the white blood cells to kill tumor cells. Giving cellular adoptive immunotherapy with aldesleukin may be a better treatment for metastatic merkel cell carcinoma.', 'detailedDescription': 'PRIMARY OBJECTIVES:\n\nI. Determine the safety and potential toxicities associated with treating patients with metastatic merkel cell carcinoma (MCC) by combined myosin heavy chain (MHC) up-regulation therapy and adoptive transfer of merkel cell polyomavirus (MCPyV) T-antigen (TAg)-specific polyclonal autologous cluster of differentiation (CD)8+ T cells.\n\nII. Determine the antitumor efficacy associated with treating patients with metastatic MCC by combined MHC up-regulation therapy and adoptive transfer of MCPyV TAg-specific polyclonal autologous CD8+ T cells.\n\nSECONDARY OBJECTIVES:\n\nI. Determine the in vivo persistence and where evaluable, migration to tumor sites of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV TAg.\n\nII. Determine the in vivo functional capacity of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV TAg.\n\nOUTLINE:\n\nPatients undergo radiation therapy or recombinant interferon beta intralesional injection within day -3 to day -1.\n\nPatients receive MCPyV TAg-specific polyclonal autologous CD8-positive T cell vaccine intravenously (IV) on day 1 and aldesleukin subcutaneously (SC) every 12 hours on days 1-14. Treatment repeats at least every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.\n\nPatients with continued presence of detectable metastatic disease 8 weeks after the first infusion may repeat the treatment regimen including radiation therapy or recombinant interferon beta injection.\n\nAfter completion of study treatment, patients are followed up every 3 months.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histopathological documentation of MCC concurrent with the diagnosis of metastatic disease\n* Evidence of MCPyV TAg tumor expression\n* Available peptide-MHC pair that can be folded into a tetramer for which MCPyV TAg-specific cells can be generated and reactivity to cell lines expressing MCPyV TAg with the corresponding human leukocyte antigen (HLA)\n* Bi-dimensionally measurable disease by palpation, clinical exam, or radiographic imaging (x-ray, computed tomography \\[CT\\] scan, positron emission tomography \\[PET\\] scan, magnetic resonance imaging \\[MRI\\], or ultrasound)\n* At least 3 weeks must have passed since any of the following: systemic corticosteroids, immunotherapy (for example, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocyte \\[TIL\\] or lymphokine-activated killer \\[LAK\\] therapy), pentoxifylline, other small molecule or chemotherapy cancer treatment, other investigational agents or other agents that target merkel cell carcinoma\n* Cardiac ejection fraction \\>= 40% (multigated acquisition \\[MUGA\\] or echocardiogram); for patients with significant risk factors for coronary artery disease (CAD) (including family history, hypertension, and/or dyslipidemia), or age \\> 50, stress echo or stress thallium testing is required\n\nExclusion Criteria:\n\n* Unable to generate antigen-specific MCPyV TAg-specific CD8+ T cells for infusions\n* Active infections prior to receiving study treatment or systemic infection requiring chronic maintenance or suppressive therapy\n* Eastern Cooperative Oncology Group (ECOG) performance status \\> 2\n* White blood cell (WBC) \\< 2000/mcl\n* Hemoglobin (Hb) \\< 8 g/dL\n* Absolute neutrophil count (ANC) \\< 1000/mcl\n* Platelets \\< 50,000/mcl\n* New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, stable or unstable angina, symptoms of coronary artery disease, congestive heart failure, clinically significant hypotension, or an ejection fraction of =\\< 40 % (echocardiogram or MUGA)\n* Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) \\< 2.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin \\[Hgb\\]) \\< 50% will be excluded\n* Creatinine clearance \\< 30 ml/min which cannot be attributed to MCC metastasis\n* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \\> 5 x upper limit of normal (ULN)\n* Bilirubin \\> 3 x ULN which cannot be attributed to MCC metastasis\n* Active autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease, inflammatory bowel disease) whose possible progression during treatment would be considered unacceptable by the investigators\n* Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1-2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 4 weeks have elapsed from the last scan\n* Any condition or organ toxicity that is deemed by the principal investigator (PI) or the attending physician to place the patient at unacceptable risk for treatment on the protocol\n* Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry\n* Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation\n* Patients may not be on any other treatments for their cancer aside from those included in the protocol; patients may not undergo another form of treatment concurrently with this study'}, 'identificationModule': {'nctId': 'NCT01758458', 'briefTitle': 'Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma', 'organization': {'class': 'OTHER', 'fullName': 'Fred Hutchinson Cancer Center'}, 'officialTitle': 'Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma', 'orgStudyIdInfo': {'id': '2586.00'}, 'secondaryIdInfos': [{'id': 'NCI-2012-02779', 'type': 'REGISTRY', 'domain': 'CTRP (Clinical Trial Reporting Program)'}, {'id': '2586'}, {'id': '2586.00', 'type': 'OTHER', 'domain': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium'}, {'id': 'P30CA015704', 'link': 'https://reporter.nih.gov/quickSearch/P30CA015704', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (autologous T cells and aldesleukin)', 'description': 'Patients undergo radiation therapy or recombinant interferon beta intralesional injection within day -3 to day -1.\n\nPatients receive MCPyV TAg-specific polyclonal autologous CD8-positive T cell infusion IV on day 1 and aldesleukin SC every 12 hours on days 1-14. Treatment repeats at least every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.\n\nPatients with continued presence of detectable metastatic disease 8 weeks after the first infusion may repeat the treatment regimen including radiation therapy or recombinant interferon beta injection.', 'interventionNames': ['Biological: Aldesleukin', 'Other: Laboratory Biomarker Analysis', 'Biological: MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells', 'Radiation: Radiation Therapy', 'Biological: Recombinant Interferon Beta']}], 'interventions': [{'name': 'Aldesleukin', 'type': 'BIOLOGICAL', 'otherNames': ['125-L-Serine-2-133-interleukin 2', 'Proleukin', 'r-serHuIL-2', 'Recombinant Human IL-2', 'Recombinant Human Interleukin-2'], 'description': 'Given SC', 'armGroupLabels': ['Treatment (autologous T cells and aldesleukin)']}, {'name': 'Laboratory Biomarker Analysis', 'type': 'OTHER', 'description': 'Correlative studies', 'armGroupLabels': ['Treatment (autologous T cells and aldesleukin)']}, {'name': 'MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells', 'type': 'BIOLOGICAL', 'description': 'Given IV', 'armGroupLabels': ['Treatment (autologous T cells and aldesleukin)']}, {'name': 'Radiation Therapy', 'type': 'RADIATION', 'otherNames': ['Cancer Radiotherapy', 'Irradiate', 'Irradiated', 'Irradiation', 'RADIATION', 'Radiotherapeutics', 'Radiotherapy', 'RT', 'Therapy, Radiation'], 'description': 'Undergo radiation therapy', 'armGroupLabels': ['Treatment (autologous T cells and aldesleukin)']}, {'name': 'Recombinant Interferon Beta', 'type': 'BIOLOGICAL', 'otherNames': ['Beta Interferon', 'Betantrone', 'Feron', 'Human Interferon Beta', 'Interferon Beta', 'Interferon, Beta', 'Interferon-B', 'Interferon-beta', 'Naferon'], 'description': 'Given intralesionally', 'armGroupLabels': ['Treatment (autologous T cells and aldesleukin)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '98109', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}], 'overallOfficials': [{'name': 'Aude Chapuis', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fred Hutchinson Cancer Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Aude Chapuis', 'investigatorAffiliation': 'Fred Hutchinson Cancer Center'}}}}