Ignite Creation Date:
2025-12-24 @ 7:47 PM
Ignite Modification Date:
2026-01-16 @ 7:23 AM
Study NCT ID:
NCT02314403
Status:
COMPLETED
Last Update Posted:
2021-10-25
First Post:
2014-12-05
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007676', 'term': 'Kidney Failure, Chronic'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}], 'ancestors': [{'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069594', 'term': 'Abatacept'}, {'id': 'D000069283', 'term': 'Rituximab'}, {'id': 'D014916', 'term': 'Whole-Body Irradiation'}, {'id': 'D016030', 'term': 'Kidney Transplantation'}], 'ancestors': [{'id': 'D018796', 'term': 'Immunoconjugates'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D058846', 'term': 'Antibodies, Monoclonal, Murine-Derived'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D011878', 'term': 'Radiotherapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D017582', 'term': 'Renal Replacement Therapy'}, {'id': 'D016377', 'term': 'Organ Transplantation'}, {'id': 'D014180', 'term': 'Transplantation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D013520', 'term': 'Urologic Surgical Procedures'}, {'id': 'D013519', 'term': 'Urogenital Surgical Procedures'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'tkawai@mgh.harvard.edu', 'phone': '617-726-0289', 'title': 'Tatsuo Kawai, MD PhD', 'organization': 'Massachusetts General Hospital'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'The incidence of adverse events found around 10 days after bone marrow transplant.'}}, 'adverseEventsModule': {'timeFrame': '5 years', 'description': 'An adverse event is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial.\n\nAn adverse event will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes first.', 'eventGroups': [{'id': 'EG000', 'title': 'Combined Bone Marrow and Kidney Transplantation', 'description': 'Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.\n\nBelatacept: A selective T-cell (lymphocyte) costimulation blocker\n\nATG: A T-Cell Depleting Agent\n\nRituximab: B-Cell Depleting Agent\n\nTotal Body Irradiation\n\nThymic Irradiation\n\nCombined Bone Marrow/Kidney Transplantation', 'otherNumAtRisk': 2, 'deathsNumAtRisk': 2, 'otherNumAffected': 2, 'seriousNumAtRisk': 2, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'HSV Lesion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Heel pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Thrombotic Microangiopathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Successful Withdrawal of Immunosuppression', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Combined Bone Marrow and Kidney Transplantation', 'description': 'Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.\n\nBelatacept: A selective T-cell (lymphocyte) costimulation blocker\n\nATG: A T-Cell Depleting Agent\n\nRituximab: B-Cell Depleting Agent\n\nTotal Body Irradiation\n\nThymic Irradiation\n\nCombined Bone Marrow/Kidney Transplantation'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '5 Years', 'description': 'The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)', 'calculatePct': False, 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Two subjects underwent conditioning regimen'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Combined Bone Marrow and Kidney Transplantation', 'description': 'Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.\n\nBelatacept: A selective T-cell (lymphocyte) costimulation blocker\n\nATG: A T-Cell Depleting Agent\n\nRituximab: B-Cell Depleting Agent\n\nTotal Body Irradiation\n\nThymic Irradiation\n\nCombined Bone Marrow/Kidney Transplantation'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Combined Bone Marrow and Kidney Transplantation', 'description': 'Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.\n\nBelatacept: A selective T-cell (lymphocyte) costimulation blocker\n\nATG: A T-Cell Depleting Agent\n\nRituximab: B-Cell Depleting Agent\n\nTotal Body Irradiation\n\nThymic Irradiation\n\nCombined Bone Marrow/Kidney Transplantation'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '37', 'spread': '5.5', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'noSap': True, 'largeDocs': [{'date': '2016-03-08', 'size': 138991, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2021-08-06T13:35', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 2}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-02'}, 'statusVerifiedDate': '2021-10', 'completionDateStruct': {'date': '2021-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-10-04', 'studyFirstSubmitDate': '2014-12-05', 'resultsFirstSubmitDate': '2021-08-06', 'studyFirstSubmitQcDate': '2014-12-08', 'lastUpdatePostDateStruct': {'date': '2021-10-25', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-08-06', 'studyFirstPostDateStruct': {'date': '2014-12-11', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-09-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Successful Withdrawal of Immunosuppression', 'timeFrame': '5 Years', 'description': 'The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['ESRD'], 'conditions': ['Kidney Failure, Chronic', 'Renal Insufficiency']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.ncbi.nlm.nih.gov/pubmed/21666482?dopt=Abstract', 'label': 'Kawai T, Cosimi AB, Sachs DH. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant. 2011 Aug;16(4):366-71.'}, {'url': 'http://www.ncbi.nlm.nih.gov/pubmed/21839648?dopt=Abstract', 'label': 'Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011 Jun;23(3):165-73.'}, {'url': 'http://www.ncbi.nlm.nih.gov/pubmed/18216355?dopt=Abstract', 'label': 'Kawai T, (et.al.) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61.'}]}, 'descriptionModule': {'briefSummary': "This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a haplo-identical related donor. An investigational medication and other treatments will be given prior to and after the transplant to help protect the transplanted kidney from being attacked by the body's immune system"}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female 18-60 years of age\n* Candidate for a living-donor renal allograft from an HLA mismatched donor\n* First or second transplant with either a living donor or cadaveric transplant as the first transplant.\n* Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation.\n* Ability to understand and provide informed consent.\n* Serologic evidence of prior exposure to EBV.\n\nExclusion Criteria:\n\n* ABO blood group-incompatible renal allograft.\n* Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by routine methodology (AHG and/or ELISA)\n* Leukopenia or thrombocytopenia.\n* Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for hepatitis B surface antigen.\n* Cardiac ejection fraction \\< 40% or clinical evidence of insufficiency.\n* Forced expiratory volume FEV1 \\< 50% of predicted.\n* Lactation or pregnancy.\n* History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.\n* Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis, type I or II membranoprolifertive glomerulonephritis).\n* Prior dose-limiting radiation therapy.\n* Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen.\n* Enrollment in other investigational drug studies within 30 days prior to enrollment.\n* Abnormal (\\>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).\n* Allergy or sensitivity to any component of belatacept, ATG, tacrolimus, or rituximab.\n* Maintenance immunosuppression within 3 months prior to conditioning other than physiological doses of steroids, defined as ≤ 50 mg of hydrocortisone or dose equivalent.\n* The presence of any medical condition that the investigator deems incompatible with participation in the trial.'}, 'identificationModule': {'nctId': 'NCT02314403', 'briefTitle': 'Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)', 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts General Hospital'}, 'orgStudyIdInfo': {'id': 'MGH Tolerance Trial'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Combined Bone Marrow and Kidney Transplantation', 'description': 'Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.', 'interventionNames': ['Drug: Belatacept', 'Drug: ATG', 'Drug: Rituximab', 'Radiation: Total Body Irradiation', 'Radiation: Thymic Irradiation', 'Procedure: Combined Bone Marrow/Kidney Transplantation']}], 'interventions': [{'name': 'Belatacept', 'type': 'DRUG', 'description': 'A selective T-cell (lymphocyte) costimulation blocker', 'armGroupLabels': ['Combined Bone Marrow and Kidney Transplantation']}, {'name': 'ATG', 'type': 'DRUG', 'description': 'A T-Cell Depleting Agent', 'armGroupLabels': ['Combined Bone Marrow and Kidney Transplantation']}, {'name': 'Rituximab', 'type': 'DRUG', 'description': 'B-Cell Depleting Agent', 'armGroupLabels': ['Combined Bone Marrow and Kidney Transplantation']}, {'name': 'Total Body Irradiation', 'type': 'RADIATION', 'armGroupLabels': ['Combined Bone Marrow and Kidney Transplantation']}, {'name': 'Thymic Irradiation', 'type': 'RADIATION', 'armGroupLabels': ['Combined Bone Marrow and Kidney Transplantation']}, {'name': 'Combined Bone Marrow/Kidney Transplantation', 'type': 'PROCEDURE', 'armGroupLabels': ['Combined Bone Marrow and Kidney Transplantation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Tatsuo Kawai, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Massachusetts General Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Surgery, Harvard Medical School', 'investigatorFullName': 'Tatsuo Kawai, MD, PhD', 'investigatorAffiliation': 'Massachusetts General Hospital'}}}}