Ignite Creation Date:
2025-12-24 @ 1:37 PM
Ignite Modification Date:
2025-12-27 @ 9:59 PM
Study NCT ID:
NCT02337595
Status:
COMPLETED
Last Update Posted:
2016-04-22
First Post:
2015-01-09
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D054218', 'term': 'Precursor T-Cell Lymphoblastic Leukemia-Lymphoma'}, {'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}, {'id': 'C565469', 'term': 'Immune Deficiency Disease'}, {'id': 'D000080983', 'term': 'Bone Marrow Failure Disorders'}, {'id': 'D009894', 'term': 'Opportunistic Infections'}, {'id': 'D006086', 'term': 'Graft vs Host Disease'}], 'ancestors': [{'id': 'D054198', 'term': 'Precursor Cell Lymphoblastic Leukemia-Lymphoma'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'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': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D007239', 'term': 'Infections'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-04', 'completionDateStruct': {'date': '2016-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-04-21', 'studyFirstSubmitDate': '2015-01-09', 'studyFirstSubmitQcDate': '2015-01-12', 'lastUpdatePostDateStruct': {'date': '2016-04-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2015-01-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cumulative incidence of grade 2-4 acute graft-versus-host disease', 'timeFrame': '100 days', 'description': 'Cumulative incidence (competing risk model) of acute graft-versus-host disease'}, {'measure': 'Immune reconstitution (Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay)', 'timeFrame': '120 days', 'description': 'Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay'}], 'secondaryOutcomes': [{'measure': '1-year survival', 'timeFrame': '1 year', 'description': 'Kaplan-Meyer estimate of overall survival'}, {'measure': 'Transplant-related mortality', 'timeFrame': '1-year', 'description': 'Cumulative incidence (competing risk model) of transplant-related mortality'}, {'measure': 'Incidence of chronic graft-versus-host disease', 'timeFrame': '1 year', 'description': 'Cumulative incidence (competing risk model) of chronic graft-versus-host disease'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['CD45RA-depletion', 'TCR-alpha/beta depletion', 'Hematopoietic Stem Cell Transplantation', 'immune reconstitution', 'Graft Enhancement, Immunologic', 'Immunocompromized Host'], 'conditions': ['Precursor T-Cell Lymphoblastic Leukemia-Lymphoma', 'Leukemia, Myeloid, Acute', 'Immune Deficiency Disease', 'Bone Marrow Failure Syndromes', 'Opportunistic Infections', 'Graft vs Host Disease']}, 'referencesModule': {'references': [{'pmid': '23933765', 'type': 'BACKGROUND', 'citation': 'Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014 Jan;49(1):138-44. doi: 10.1038/bmt.2013.114. Epub 2013 Aug 12.'}, {'pmid': '24525279', 'type': 'BACKGROUND', 'citation': 'Bleakley M, Heimfeld S, Jones LA, Turtle C, Krause D, Riddell SR, Shlomchik W. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol Blood Marrow Transplant. 2014 May;20(5):705-16. doi: 10.1016/j.bbmt.2014.01.032. Epub 2014 Feb 11.'}]}, 'descriptionModule': {'briefSummary': 'The stud will evaluate whether infusions of CD45RA-depleted lymphocytes from the donor early post-transplant is a safe way to improve immunity to common infections in recipients of TCR-alpha/beta depleted hematopoietic stem cell grafts.', 'detailedDescription': 'Graft-versus-host disease (GVHD) remains the most important direct complication of hematopoietic stem cell transplantation. Methods used to prevent GVHD include diverse pharmacologic interventions and ex vivo methods of T-cell depletion, the latter being the most effective ones. Historically depletion of T-cells from the graft is associated with increased rate of graft failure, relapse of malignant disease and prolonged immune deficiency. Selective depletion of TCR-alpha/beta T-lymphocytes is a new method of hematopoietic stem cell graft manipulation which is thought to conserve important cell populations, e.g. NK cells and gamma/delta T cells within the graft. Preliminary results suggest that TCR alpha/beta depletion ensures high engraftment rate, low early mortality and good control of GVHD. The problem of delayed immune reconstitution and life-threatening viral infections remains incompletely resolved.\n\nDepletion of naive (CD45RA-positive) T-cells was developed as a new method of graft manipulation to prevent GVHD. Research data indicate that alloreactivity is associated mainly with naive T-cell fraction. In vitro depletion of CD45RA lowers significantly the alloreactive response while retaining reactivity to pathogens.\n\nIn the current protocol we plan to test whether relatively low doses of CD45RA-depleted mononuclear cells can be safely infused after TCR-alpha/beta depleted transplantation. The biologic readout for the protocol will be quantitative assessment of T-cell reactivity to common pathogens after infusion.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '25 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* recipient of allogeneic hematopoietic stem cell graft from haploidentical or matched unrelated donor\n* TCR alpha/beta depletion of the hematopoietic stem cell graft\n* CMV-seropositive donor\n* stable hematopoietic engraftment\n\nExclusion Criteria:\n\n* active graft-versus-host disease grade 2-4\n* any systemic immune suppressive therapy except calcineurin inhibitor monotherapy\n* uncontrolled sepsis'}, 'identificationModule': {'nctId': 'NCT02337595', 'acronym': '45RA_NEG_DLI', 'briefTitle': 'Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation', 'organization': {'class': 'OTHER', 'fullName': 'Federal Research Institute of Pediatric Hematology, Oncology and Immunology'}, 'officialTitle': 'Transfusion of CD45RA-depleted Donor Lymphocytes to Improve Regeneration of Antimicrobial Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation', 'orgStudyIdInfo': {'id': 'CD45RA_NEG_DLI_2014FRCPHOI'}}, 'armsInterventionsModule': {'interventions': [{'name': 'CD45RA-depleted peripheral blood mononuclear cells', 'type': 'BIOLOGICAL', 'description': 'Infusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells'}]}, 'contactsLocationsModule': {'locations': [{'zip': '117997', 'city': 'Moscow', 'country': 'Russia', 'facility': 'Federal Research Center for pediatric hematology, oncology and immunology', 'geoPoint': {'lat': 55.75204, 'lon': 37.61781}}], 'overallOfficials': [{'name': 'Michael Maschan, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Fedaral Research Center for pediatric hematology, oncology and immunology'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Federal Research Institute of Pediatric Hematology, Oncology and Immunology', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}