Ignite Creation Date:
2025-12-25 @ 12:04 AM
Ignite Modification Date:
2026-04-17 @ 12:17 AM
Study NCT ID:
NCT00500058
Status:
COMPLETED
Last Update Posted:
2017-07-26
First Post:
2007-07-10
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D009369', 'term': 'Neoplasms'}], 'ancestors': [{'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020382', 'term': 'Interleukin-18'}, {'id': 'D000069283', 'term': 'Rituximab'}], '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': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D058846', 'term': 'Antibodies, Monoclonal, Murine-Derived'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-07-31', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-07', 'completionDateStruct': {'date': '2010-03-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-07-24', 'studyFirstSubmitDate': '2007-07-10', 'studyFirstSubmitQcDate': '2007-07-10', 'lastUpdatePostDateStruct': {'date': '2017-07-26', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2007-07-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-03-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks', 'timeFrame': '12 weeks'}], 'secondaryOutcomes': [{'measure': 'assess blood values of combination treatment for 4 weeks assess blood values of SB-485232 for additional 8 weeks', 'timeFrame': '12 weeks'}, {'measure': 'Pharmacokinetic parameters for SB-485232 and Rituxan: AUCtau, Cmax, and Cmin.', 'timeFrame': '12 weeks'}, {'measure': 'Pharmacodynamic biomarker responses:', 'timeFrame': '12 weeks'}, {'measure': 'Plasma IFN-γ, GMCSF, IP-10, MIG, and MCP-1 changes', 'timeFrame': 'from baseline and predose'}, {'measure': 'Plasma IL-18BP change', 'timeFrame': 'from baseline'}, {'measure': 'PBMC phenotype changes', 'timeFrame': 'from baseline and pre-dose'}, {'measure': 'Activated NK cells (CD16+/CD56+/CD3-/CD69+/FasL+ or IL-18Ra+)', 'timeFrame': '12 weeks'}, {'measure': 'Activated cytolytic T cells (CD8+/CD4-/CD3+/CD69+ FasL+ or IL- 18Ra+)', 'timeFrame': '12 weeks'}, {'measure': 'Activated B cells (CD19+/CD25-/CD3-/CD69+)', 'timeFrame': '12 weeks'}, {'measure': 'Activated Neutrophils/Monocytes (CD11b+/CD16+/CD64+/CD14+/CD45+/CD69+)', 'timeFrame': '12 weeks'}, {'measure': 'Regulatory T-cells (FoxP3+/CD25+/CD4+/CD127+)', 'timeFrame': '12 weeks'}, {'measure': 'Immunogenicity (anti-SB-485232 and anti-Rituximab antibodies)', 'timeFrame': '12 weeks'}, {'measure': 'Anti-tumor activity (Radiographic tumor assessments)', 'timeFrame': '12 weeks'}, {'measure': 'CD16 (FcγRIIIA) 158V/F genotyping', 'timeFrame': '12 weeks'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Rituximab,', 'oncology', 'IL-18,', 'combination study,', 'cytokine,'], 'conditions': ['Lymphoma, Non-Hodgkin']}, 'referencesModule': {'availIpds': [{'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Study Protocol', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}, {'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Annotated Case Report Form', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}, {'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Informed Consent Form', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}, {'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Statistical Analysis Plan', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}, {'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Individual Participant Data Set', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}, {'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Clinical Study Report', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}, {'id': 'ILI105618', 'url': 'https://www.clinicalstudydatarequest.com', 'type': 'Dataset Specification', 'comment': 'For additional information about this study please refer to the GSK Clinical Study Register'}], 'references': [{'pmid': '23799412', 'type': 'BACKGROUND', 'citation': 'Robertson MJ, Kline J, Struemper H, Koch KM, Bauman JW, Gardner OS, Murray SC, Germaschewski F, Weisenbach J, Jonak Z, Toso JF. A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-Hodgkin lymphoma. J Immunother. 2013 Jul-Aug;36(6):331-41. doi: 10.1097/CJI.0b013e31829d7e2e.'}], 'seeAlsoLinks': [{'url': 'https://gsk-clinicalstudyregister.com/study/ILI105618?search=study&search_terms=ILI105618#rs', 'label': 'Results for study ILI105618 can be found on the GSK Clinical Study Register.'}, {'url': 'https://www.clinicalstudydatarequest.com', 'label': 'Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.'}]}, 'descriptionModule': {'briefSummary': "The purpose is to identify a dose of SB-485232 which is safe, tolerable and effective when used in combination with Rituximab in patients with non-Hodgkin's lymphoma (NHL). This study will use a standard treatment regimen of Rituximab in combination with rising doses of SB-485232. The dose selected from this study will be used in a future studies."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Histologically confirmed diagnosis of any subtype of CD20+ B cell NHL. Subjects must have disease that progressed after standard therapy or for which there is no effective standard therapy (including high-dose therapy and autologous stem cell transplantation). NOTE: If the subject has had a prior autologous stem cell transplant, it must have occurred at least three months prior to screening and the subject must be fully recovered from any acute toxicities.\n* Prior treatment with Rituximab is allowed, provided it was completed at least six months before study enrollment.\n* Male or female ≥ 18 years of age.\n* Measurable or evaluable disease.\n* Predicted life expectancy of at least 12 weeks.\n* ECOG Performance Status of 0 or 1.\n* No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer, radiotherapy, or surgical procedures (except for minor surgical procedures) within four weeks before beginning treatment with SB-485232 (6 weeks for nitrosoureas and mitomycin C). Subjects must have recovered from toxicities (incurred as a result of previous therapy) sufficiently to be entered into a Phase I study.\n* A signed and dated written informed consent form is obtained from the subject.\n* The subject is able to understand and comply with protocol requirements, timetables, instructions and protocol-stated restrictions.\n\nThe subject is likely to maintain good venous blood access for PK and PD sampling throughout the study.\n\n* A female is eligible to enter and participate in the study if she is of:\n\n a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:\n* has had a hysterectomy,\n* has had a bilateral oophorectomy (ovariectomy),\n* has had a bilateral tubal ligation,\n* is post-menopausal (demonstrate total cessation of menses for greater than 1year), If amenorrheic for less than one year, post-menopausal status will be confirmed by serum follicle stimulating hormone (FSH) and oestradiol concentrations at screening. or, b. childbearing potential, has a negative serum pregnancy test at the Screen Visit, and agrees to one of the following GSK acceptable contraceptive methods:\n* any intrauterine device (IUD) with a documented failure rate of less than\n\n 1% per year.\n* vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.\n* oral contraceptive (either combined or progesterone only).\n* because of the unacceptable failure rate of barrier (chemical and/or physical) methods, the barrier method of contraception must only be used in combination with other acceptable methods described above.\n* Adequate organ function,\n\nExclusion Criteria:\n\n* Women who are pregnant or are breast-feeding.\n* Significant cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or autoimmune conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.\n* The subject has diabetes mellitus with poor glycemic control.\n* The subject has a history of human immunodeficiency virus (HIV) or other immunodeficiency disease.\n* The subject has positive Hepatitis B surface antigen.\n* Corrected QT interval (QTc) \\> 480msec.\n* The subject has a history of a severe infusion related reaction or tumor lysis syndrome following treatment with Rituximab (Section 10.2.2).\n* The subject has a circulating malignant cell count \\> 25,000/mm3 in peripheral blood.\n* The subject has known anaphylaxis or IgE-mediated hypersensitivity to murine proteins.\n* The subject has an acute infection or severe or uncontrolled infections requiring systemic antibiotic therapy.\n* Any serious medical or psychiatric disorder that would interfere with subject safety or informed consent.\n* Known leptomeningeal disease or evidence of prior or current metastatic brain disease. Routine screening with central nervous system (CNS) imaging studies (CT or MRI) is required only if clinically indicated.\n* Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.\n* Oral corticosteroids within 14 days of study entry.\n* History of alcohol abuse within six months of screening or alcohol consumption in the past six months exceeding seven drinks/week for women and 14 drinks/week for men (where 1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).\n* History of ventricular arrhythmias requiring drug or device therapy.\n* Any unresolved or unstable serious toxicity from prior administration of another investigational drug.\n* Any investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of SB-485232.\n* Donation of blood in excess of 500 mL within a 56-day period prior to dosing."}, 'identificationModule': {'nctId': 'NCT00500058', 'briefTitle': 'A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18', 'organization': {'class': 'INDUSTRY', 'fullName': 'GlaxoSmithKline'}, 'officialTitle': 'A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18 (SB-485232) Administered by Intravenous Infusion in Combinationwith Rituximab in Adult Patients With B Cell Non-Hodgkin\'sLymphoma"', 'orgStudyIdInfo': {'id': 'ILI105618'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'SB-485232+Rituximab', 'description': 'Rituximab 375 milligrams per square meter (mg/m\\^2) will be administered to subjects with CD20+ B cell lymphoma by intravenous (IV) infusion once a week for four consecutive weeks on Day 1 of Weeks 1 to 4. SB-485232 will be administered by IV infusion over a 2 hour period, at doses ranging from 1 microgram (μg)/kilogram (kg) to 100 μg/kg. SB-485232 will be given once a week for 12 consecutive weeks on Day 2 of Weeks 1 to 4 and Day 2 (± 1 day) of Weeks 5 to 12. SB-485232 will be infused at least 24 hours after the Rituximab infusion was started.', 'interventionNames': ['Drug: SB-485232', 'Drug: Rituximab']}], 'interventions': [{'name': 'SB-485232', 'type': 'DRUG', 'description': 'SB-485232 for injection, 7 mg/vial, will be available as a lyophilized cake. It will be reconstituted with 1.4 mL of water for injection. Each vial of this drug product is a clear, colorless solution containing 5 mg/mL of SB-485232.', 'armGroupLabels': ['SB-485232+Rituximab']}, {'name': 'Rituximab', 'type': 'DRUG', 'description': 'Rituximab 375 mg/m\\^2 will be administered by IV infusion.', 'armGroupLabels': ['SB-485232+Rituximab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '60637', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'GSK Investigational Site', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '46202', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'GSK Investigational Site', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}], 'overallOfficials': [{'name': 'GSK Clinical Trials', 'role': 'STUDY_DIRECTOR', 'affiliation': 'GlaxoSmithKline'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'GlaxoSmithKline', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}