Ignite Creation Date:
2025-12-24 @ 6:56 PM
Ignite Modification Date:
2025-12-30 @ 8:15 PM
Study NCT ID:
NCT00319657
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2021-06-18
First Post:
2006-04-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D033581', 'term': 'Stem Cell Transplantation'}], 'ancestors': [{'id': 'D017690', 'term': 'Cell Transplantation'}, {'id': 'D064987', 'term': 'Cell- and Tissue-Based Therapy'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D014180', 'term': 'Transplantation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Combined hematopoietic stem cell and kidney transplantation'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 15}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2004-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-06', 'completionDateStruct': {'date': '2026-07', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2021-06-15', 'studyFirstSubmitDate': '2006-04-28', 'studyFirstSubmitQcDate': '2006-04-28', 'lastUpdatePostDateStruct': {'date': '2021-06-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2006-04-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2026-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Discontinuation of maintenance immunosuppressive drugs', 'timeFrame': 'Measured at 12 months', 'description': 'Study subjects are discontinued from immunosuppressive drugs as they have achieved immune tolerance at 12 months'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Kidney Transplantation', 'Blood Stem Cell Transplantation'], 'conditions': ['Immune Tolerance']}, 'referencesModule': {'references': [{'pmid': '10836360', 'type': 'BACKGROUND', 'citation': 'Strober S, Benike C, Krishnaswamy S, Engleman EG, Grumet FC. Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity. Transplantation. 2000 Apr 27;69(8):1549-54. doi: 10.1097/00007890-200004270-00005.'}, {'pmid': '12023614', 'type': 'BACKGROUND', 'citation': 'Millan MT, Shizuru JA, Hoffmann P, Dejbakhsh-Jones S, Scandling JD, Grumet FC, Tan JC, Salvatierra O, Hoppe RT, Strober S. Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation. Transplantation. 2002 May 15;73(9):1386-91. doi: 10.1097/00007890-200205150-00005.'}, {'pmid': '21991976', 'type': 'RESULT', 'citation': 'Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med. 2011 Oct 6;365(14):1359-60. doi: 10.1056/NEJMc1107841. No abstract available.'}, {'pmid': '22405058', 'type': 'RESULT', 'citation': 'Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant. 2012 May;12(5):1133-45. doi: 10.1111/j.1600-6143.2012.03992.x. Epub 2012 Mar 8.'}, {'pmid': '34432869', 'type': 'DERIVED', 'citation': 'Jensen KP, Hongo DA, Ji X, Zheng P, Pawar R, Wu TH, Busque S, Scandling JD, Shizuru JA, Lowsky R, Shori A, Dutt S, Waters J, Saraswathula A, Baker J, Tamaresis JS, Lavori P, Negrin R, Maecker H, Engleman EG, Meyer E, Strober S. Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients. Blood Adv. 2021 Sep 14;5(17):3290-3302. doi: 10.1182/bloodadvances.2020003669.'}]}, 'descriptionModule': {'briefSummary': 'The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone Marrow Transplantation are enrolling patients into a research study to determine if blood stem cells injected after kidney transplantation, in combination with lymphoid irradiation ,will change the immune system such that immunosuppressive drugs can be completely withdrawn. Patients must have a healthy, completely human leukocyte antigen (HLA)-matched brother or sister as the organ and stem cell donor.\n\nOne to two months before kidney transplant surgery, blood stem cells will be removed from the donor and the cells will be frozen. After transplant surgery, the recipient will receive radiation and anti-T cell antibody treatments for two weeks to prepare for injection of the stem cells. The stem cells will be injected at the end of the two-week treatment. If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at least six months after transplantation. Patients will be followed in the Stanford clinics for transplant patients. Patients who live outside of the San Francisco Bay Area must remain near Stanford for six weeks after transplant surgery.', 'detailedDescription': 'The purpose of this study is to determine the proportion of patients that can be withdrawn completely from immunosuppressive drugs while maintaining normal function of HLA-matched living related donor kidney transplants. Fifteen participants will be conditioned with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (ATG), and given an infusion of donor "mobilized" blood mononuclear cells prior to transplantation.\n\nThis is a single-center, open-label study in adult renal transplant patients. Fifteen patients will receive TLI, ATG, and an infusion of CD34+ selected G-CSF mobilized blood cells combined with a fixed number (1x10\\^6) of CD3+ T cells from the same mobilized blood cell source. Patients will receive a one-month course of mycophenolate mofetil and a six to 12 month tapering course of cyclosporine that will be discontinued at six months. At serial timepoints (1) graft function will be monitored, (2) chimerism will be measured in recipient white blood cell subsets, (3) mixed lymphocyte response (MLR) assays of peripheral blood mononuclear cells against donor and third party cells will be performed, and (4) protocol biopsies of the graft will be obtained. An attempt will be made to discontinue cyclosporine at six months if (1) chimerism is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) there is stable graft function without clinical rejection episodes, and (3) there is lack of histologic rejection on protocol biopsies. In the proposed study, patients will be given a target dose of 8-10x10\\^6 CD34+ cells/kg and 1x10\\^6 CD3+ cells/kg because sustained chimerism may be necessary for sustained tolerance to the graft.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Kidney transplant performed at Stanford University Medical Center\n* Have an HLA-matched sibling donor\n* No known contraindication to administration of rabbit ATG or radiation\n* Willing to use a reliable form of contraception for at least 24 months following transplantation\n\nExclusion Criteria:\n\n* Previous treatment with rabbit ATG or a known allergy to rabbit proteins\n* History of cancer, other than non-melanoma skin cancer\n* Pregnant or breastfeeding\n* HIV, Hepatitis B, or Hepatitis C infection\n* Previous organ transplant\n* Leukopenia (white blood cell count less than 3000/mm³)\n* Thrombocytopenia (platelet count less than 100,000/mm³)\n* cPRA\\>80%'}, 'identificationModule': {'nctId': 'NCT00319657', 'briefTitle': 'Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs', 'organization': {'class': 'OTHER', 'fullName': 'Stanford University'}, 'officialTitle': 'Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-Cell Transfusion in HLA-Matched Living Donor Kidney Transplantation', 'orgStudyIdInfo': {'id': '367'}, 'secondaryIdInfos': [{'id': 'P01HL075462-02', 'link': 'https://reporter.nih.gov/quickSearch/P01HL075462-02', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Immune tolerance, kidney transplantation', 'description': 'Intervention: Participants will receive hematopoietic cell transplantation and Total lymphoid irradiation. The intervention is intended to induce immune tolerance in HLA-matched living donor kidney transplantation, to allow withdrawal of the immunosuppressive drugs. Immune tolerance is achieved through the development of donor/recipient mixed chimerism following combined kidney and hematopoietic stem cell transplantation from the living donor.', 'interventionNames': ['Biological: Hematopoietic cell transplantation', 'Radiation: Total lymphoid irradiation']}], 'interventions': [{'name': 'Hematopoietic cell transplantation', 'type': 'BIOLOGICAL', 'description': 'Transplantation of hematopoietic stem cells from the living donor.', 'armGroupLabels': ['Immune tolerance, kidney transplantation']}, {'name': 'Total lymphoid irradiation', 'type': 'RADIATION', 'description': 'Total lymphoid irradiation is used as part of the conditioning regimen for the hematopoietic stem cell transplant.', 'armGroupLabels': ['Immune tolerance, kidney transplantation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94305', 'city': 'Stanford', 'state': 'California', 'country': 'United States', 'facility': 'Stanford University, School of Medicine', 'geoPoint': {'lat': 37.42411, 'lon': -122.16608}}], 'overallOfficials': [{'name': 'Samuel Strober, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Stanford University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Individual Patient Data will not be shared'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Stanford University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Chair of Study', 'investigatorFullName': 'Samuel Strober', 'investigatorAffiliation': 'Stanford University'}}}}