Ignite Creation Date:
2025-12-24 @ 10:35 PM
Ignite Modification Date:
2025-12-31 @ 8:23 AM
Study NCT ID:
NCT01086735
Status:
COMPLETED
Last Update Posted:
2013-01-14
First Post:
2010-03-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019337', 'term': 'Hematologic Neoplasms'}, {'id': 'D012008', 'term': 'Recurrence'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 11}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-01', 'completionDateStruct': {'date': '2012-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-01-11', 'studyFirstSubmitDate': '2010-03-12', 'studyFirstSubmitQcDate': '2010-03-12', 'lastUpdatePostDateStruct': {'date': '2013-01-14', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-03-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV', 'timeFrame': 'during the 12 months of follow-up', 'description': 'Incidence of "severe" GHVD (acute grade \\>II or chronic extensive) following DLI-TK and treatment with GCV'}], 'secondaryOutcomes': [{'measure': 'The incidence of GVHD of any grade after DLI-TK', 'timeFrame': 'during the 12 months of follow-up', 'description': 'The incidence of GVHD of any grade after DLI-TK'}, {'measure': 'The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy', 'timeFrame': 'during the 12 months of follow-up', 'description': 'The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy'}, {'measure': 'The survival and the survival without disease after DLI-TK', 'timeFrame': 'during the 12 months of follow-up', 'description': 'The survival and the survival without disease after DLI-TK'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['hematological malignancy', 'allogeneic hematopoietic stem cell transplantation', 'donor lymphocyte infusion', 'antitumor immunotherapy', 'graft-versus-tumor effect', 'gene therapy', 'relapse', 'adult'], 'conditions': ['Hematological Malignancy']}, 'descriptionModule': {'briefSummary': 'The main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. We have developed a strategy of alloreactive T-cell depletion, using T-cells expressing the Herpes simplex thymidine kinase (TK) suicide gene combined with a ganciclovir (GCV) treatment. This system permits the selective elimination of dividing TK+ T-cells in vivo. To test this hypothesis in preclinical settings, we have previously developed several experimental models of GVHD using TK+ T-cells in mice. The demonstration that a preventive treatment with GCV administered close to the time of HSCT could control GVHD brought the proof of concept. We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment.', 'detailedDescription': 'DLI-TK is administered either after failure of 1 or several previous standard (std-) DLI of, defined after a minimal follow-up of 2 months after the last injection. To prepare DLI-TK, donor T-cells are transduced with a retroviral vector encoding TK. Transduced cells are selected using a CliniMACS device (MYLTENYI). In case of previous std-DLI received, the DLI-TK cell dose is adjusted to be below or equal to the maximal cell dose previously received in std-DLI. No comparison is planned in the analysis.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Hematological malignancy.\n* Previous allogeneic hematopoietic stem cell transplantation.\n* Relapse diagnosed at the molecular, cytogenetic, or cytological level.\n* Failure of a previous stdILD or inclusion in first intention without previous stdDLI.\n* Age \\> 18 years and \\< 70 years at the time of inclusion. For patients between 15 and 18 years of age, a case-per case inclusion will be studied.\n* Performance status considered on the score Eastern Cooperative Oncology Group (ECOG) \\< 2.\n* Life expectation 1-month-old superior.\n* Signed written informed consent.\n* Negative human chorionic gonadotropin (HCG) in the 7 days preceding the inclusion for women in age of procreation.\n* Membership of the French national insurance.\n\nExclusion Criteria:\n\n* Grade \\>II acute GVHD or chronic extensive GVHD at the time of inclusion.\n* Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.\n* Dysfunction of liver (alanine aminotransferase / aspartate transaminase (ALAT/ASAT) \\> 5 N, or bilirubin \\> 50 µM), or of the renal function (creatinine clearance \\< 30 ml / min).'}, 'identificationModule': {'nctId': 'NCT01086735', 'acronym': 'ILD-TK01', 'briefTitle': 'Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study', 'orgStudyIdInfo': {'id': 'P010506'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'donor lymphocyte infusion', 'description': 'Donor T-cell transduction', 'interventionNames': ['Biological: donor lymphocyte infusion']}], 'interventions': [{'name': 'donor lymphocyte infusion', 'type': 'BIOLOGICAL', 'description': 'Donor T-cell transduction', 'armGroupLabels': ['donor lymphocyte infusion']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94', 'city': 'Créteil', 'country': 'France', 'facility': 'Groupe Hospitalier Albert Chenevier-Henri Mondor', 'geoPoint': {'lat': 48.79266, 'lon': 2.46569}}], 'overallOfficials': [{'name': 'Sébastien Maury, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistance Publique - Hôpitaux de Paris'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'Paris 12 Val de Marne University', 'class': 'OTHER'}, {'name': 'Pierre and Marie Curie University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}