Ignite Creation Date:
2025-12-24 @ 9:42 PM
Ignite Modification Date:
2025-12-25 @ 7:23 PM
Study NCT ID:
NCT00306332
Status:
TERMINATED
Last Update Posted:
2009-08-18
First Post:
2006-03-22
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}, {'id': 'D015464', 'term': 'Leukemia, Myelogenous, Chronic, BCR-ABL Positive'}, {'id': 'D008223', 'term': 'Lymphoma'}], 'ancestors': [{'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D009196', 'term': 'Myeloproliferative Disorders'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 250}}, 'statusModule': {'whyStopped': 'Interim analysis has shown that the objectives of this study can not be reached', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2006-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2009-08', 'lastUpdateSubmitDate': '2009-08-17', 'studyFirstSubmitDate': '2006-03-22', 'studyFirstSubmitQcDate': '2006-03-22', 'lastUpdatePostDateStruct': {'date': '2009-08-18', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2006-03-23', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'relapse'}, {'measure': 'event-free survival'}, {'measure': 'survival'}], 'secondaryOutcomes': [{'measure': 'clinical relevance of mHag-specific CTL responses for the GVL effect'}, {'measure': 'Kinetics of NK-cel reconstitution'}, {'measure': 'Differences in NK-cell repertoire'}, {'measure': 'NK cell mediated anti tumor reactivity'}]}, 'conditionsModule': {'keywords': ['Allogeneic Stem cell transplantation', 'T-cell depletion', 'B-cell depletion', 'Immunomagnetic selection'], 'conditions': ['Leukemia, Myeloid', 'Leukemia, Lymphocytic', 'Myelodysplastic Syndrome', 'Leukemia, Myeloid, Chronic', 'Lymphoma']}, 'referencesModule': {'references': [{'pmid': '9332335', 'type': 'BACKGROUND', 'citation': 'Schaap N, Schattenberg A, Bar B, Preijers F, Geurts van Kessel A, van der Maazen R, de Boo T, de Witte T. Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. Br J Haematol. 1997 Sep;98(3):750-9. doi: 10.1046/j.1365-2141.1997.d01-3499.x.'}, {'pmid': '10918401', 'type': 'BACKGROUND', 'citation': 'Schattenberg A, Schaap N, Preijers F, van der Maazen R, de Witte T. Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant. 2000 Jul;26(1):17-22. doi: 10.1038/sj.bmt.1702451.'}, {'pmid': '11516094', 'type': 'BACKGROUND', 'citation': 'Schaap N, Schattenberg A, Bar B, Preijers F, van de Wiel van Kemenade E, de Witte T. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia. 2001 Sep;15(9):1339-46. doi: 10.1038/sj.leu.2402203.'}]}, 'descriptionModule': {'briefSummary': "T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by using immunomagnetic negative and positive selection procedures\n\nBackground:\n\nRemoval of T-cells from the donor graft (T-cell depletion) offers the possibility for prevention of GVHD and subsequently less transplant related morbidity and mortality after allogeneic stem cell transplantation (SCT). There are several techniques to deplete T-cells from the stem cell grafts e.g. physical, immunological and combined physical / immunological separation methods. All these techniques result in a stem cell graft with sufficient CD34+ stem cells combined with an adequate depletion of T and B cells. CD34+ selected stem cell grafts are very pure and do not contain any additional cell populations. In contrast, CD3+/CD19+ depleted grafts still contain NK-cells, monocytes and dendritic cells that are part of the innate immune system. Theoretically,the presence of these cells may positively influence immunological reconstitution and the graft-versus-leukaemia (GVL) effect, respectively, resulting in improved outcome after SCT\n\nObjectives:\n\nTo evaluate the differences in immunological reconstitution, transplant related mortality, disease-free survival and overall survival after T-cell depleted allogeneic SCT for haematological malignancies using either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion using the CliniMACS system in approximately 270 consecutive patients.\n\nAdditionally in this study in 20 consecutive patients the kinetics of NK-cel reconstitution and differences in NK-cell repertoire will be monitored. NK-cell mediated anti-tumor reactivity will be monitored in patients transplanted with and without NK-cells in the stem cell graft (CD3+/CD19+ depletion, versus CD34+ selection). Secondary objectives are to evaluate the clinical relevance of minor histocompatibility-specific cytotoxic T-cell responses for the GVL effect, the kinetics of NK-cell reconstitution and differences in NK-cell repertoire using the different T-cell depletion protocols.\n\nDesign:\n\nSingle center prospective randomised phase III study\n\nPopulation:\n\nPatients eligible for allogeneic SCT according to the standard criteria of our institution who will receive an allogeneic T- and B-cell depleted SCT with peripheral stem cells of an HLA-identical sibling donor or an HLA-identical unrelated voluntary (VUD) donor.\n\nIntervention:\n\nT-cell depletion will be conducted using two different techniques: either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion.\n\nEndpoints:\n\nPrimary endpoints are immunological reconstitution, relapse, disease free survival and overall survival. Secondary endpoints: NK-cell reconstitution and NK-cell mediated anti-tumour reactivity. Cytotoxic T-cell responses for the GVL effect.\n\nEstimated efforts and risks for participating patients:\n\nWe don't expect any extra patient efforts or risks because T-cell depletion is a standard procedure in our clinic for many years. There is extensive experience with immunological T-cell depletion techniques. We hypothesize CD3+/CD19+ depletion will favour stem cell transplant outcome. Immunological and molecular biological studies will be performed on blood samples already obtained as part of the standard protocol."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients with the diagnosis of:\n\n * De novo acute myeloid leukaemia in first or second remission.\n * Secondary acute myeloid leukaemia in first or second remission supervening after myelodysplastic syndrome or cytotoxic / immunosuppressive therapy.\n * Acute lymphoblastic leukaemia in first or second remission.\n * Myelodysplastic syndrome.\n * Chronic myeloid leukaemia, patients who are candidate for SCT.\n * Malignant lymphoma following relapse or first line therapy resistant.\n * Aggressive mantle cell lymphoma in first complete remission.\n* Age 18-65 years.\n* WHO performance 0-1 (see appendix ).\n* Availability of an HLA-identical sibling or HLA, A, B, DRB, DQB -identical VUD donor.\n* Life expectancy \\> 3 months.\n* Witnessed written informed consent.\n\nExclusion Criteria:\n\n* Patients with severe cardiac dysfunction (NYHA-classification II-IV)\n* Patients with severe pulmonary dysfunction (vital capacity or diffusion \\< 70% of predicted value).\n* Patients with hepatic dysfunction, bilirubin or transaminases \\> 2.5 x upper normal limit\n* Patients with renal dysfunction, serum creatinin \\> 150 umol/liter or clearance \\< 40 ml/minute.\n* Patients with a history of moderate ore severe CNS disturbances and psychiatric problems.\n* Prior treatment with chemotherapy, immunotherapy, radiation therapy or surgery within the last 3 weeks before entering the study.\n* Patients with active uncontrolled infections.\n* Patients who are poor medical risks because of non malignant systemic disease.\n* Patients with severe coagulopathy.\n* Patients to be known HIV positive.'}, 'identificationModule': {'nctId': 'NCT00306332', 'briefTitle': 'T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation', 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': 'T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures', 'orgStudyIdInfo': {'id': 'PSCT10'}}, 'armsInterventionsModule': {'interventions': [{'name': 'T-cell and B-cell depletion', 'type': 'PROCEDURE'}]}, 'contactsLocationsModule': {'locations': [{'zip': '6500 HB', 'city': 'Nijmegen', 'country': 'Netherlands', 'facility': '476 Hematology, University Medical Centre St Radboud Nijmegen', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}], 'overallOfficials': [{'name': 'Nicolaas Schaap, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud University Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Radboud University Medical Center', 'class': 'OTHER'}}}}