Ignite Creation Date:
2025-12-25 @ 12:04 AM
Ignite Modification Date:
2025-12-25 @ 10:02 PM
Study NCT ID:
NCT01475058
Status:
COMPLETED
Last Update Posted:
2017-02-15
First Post:
2011-11-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D054198', 'term': 'Precursor Cell Lymphoblastic Leukemia-Lymphoma'}, {'id': 'D016403', 'term': 'Lymphoma, Large B-Cell, Diffuse'}, {'id': 'D016400', 'term': 'Lymphoma, Large-Cell, Immunoblastic'}, {'id': 'D020522', 'term': 'Lymphoma, Mantle-Cell'}, {'id': 'D015451', 'term': 'Leukemia, Lymphocytic, Chronic, B-Cell'}], 'ancestors': [{'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': 'D016393', 'term': 'Lymphoma, B-Cell'}, {'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D015448', 'term': 'Leukemia, B-Cell'}, {'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': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-02', 'dispFirstSubmitDate': '2017-01-31', 'completionDateStruct': {'date': '2014-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-02-14', 'studyFirstSubmitDate': '2011-11-10', 'dispFirstSubmitQcDate': '2017-02-14', 'studyFirstSubmitQcDate': '2011-11-16', 'dispFirstPostDateStruct': {'date': '2017-02-15', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2017-02-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2011-11-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and toxicity assessment of study treatment', 'timeFrame': 'Up to day 42 after the T cell infusion', 'description': 'Incidence of grade \\>= 3 toxicity, as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 occurring from the T cell infusion through day 42 after the T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the T cell infusion). Incidence of acute GVHD occurring from the T cell infusion through day 42 after the T cell infusion will be assessed.'}, {'measure': 'Feasibility assessment of study treatment', 'timeFrame': 'Up to 5 years', 'description': 'If the prescribed T cell dose is delivered in more than 50% of the patients, this approach will be considered feasible for further study to reduce relapse after allogeneic HCT.'}], 'secondaryOutcomes': [{'measure': 'Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells', 'timeFrame': 'Up to 15 years'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia', 'Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia', 'Recurrent Adult Acute Lymphoblastic Leukemia', 'Recurrent Adult Diffuse Large Cell Lymphoma', 'Recurrent Adult Immunoblastic Large Cell Lymphoma', 'Recurrent Mantle Cell Lymphoma', 'Refractory Chronic Lymphocytic Leukemia']}, 'referencesModule': {'references': [{'pmid': '34515338', 'type': 'DERIVED', 'citation': 'Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.'}]}, 'descriptionModule': {'briefSummary': 'This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.', 'detailedDescription': 'PRIMARY OBJECTIVES:\n\nI. To assess the safety and feasibility of pre-emptive adoptive T cell therapy using ex vivo expanded cytomegalovirus (CMV)- or Epstein-Barr virus (EBV)-specific T cells derived from donor CD62L+ central memory (TCM) cells and genetically modified to express a CD19-specific chimeric antigen receptor (CAR) in patients in complete remission after human leukocyte antigen (HLA)-matched related donor hematopoietic stem cell transplantation (HCT) for CD19+ B cell malignancies at high risk of post-HCT relapse. (Cohort A)\n\nII. To assess the safety and feasibility of adoptive T cell therapy using ex vivo expanded CMV- or EBV-specific T cells derived from donor CD62L+ TCM cells and genetically modified to express a CD19-specific CAR in patients with persistent, progressive or relapsed disease after HLA-matched related donor HCT for CD19+ B cell malignancies. (Cohort B)\n\nSECONDARY OBJECTIVES:\n\nI. To determine the duration of in vivo persistence of adoptively transferred bi-specific CD8+ T cells, and the phenotype of persisting T cells.\n\nII. To determine if adoptively transferred bi-specific CD8+ T cells traffic to the bone marrow and function in vivo.\n\nIII. To determine if adoptively transferred bi-specific CD8+ T cells proliferate in allogeneic HCT recipients that reactivate CMV or EBV.\n\nIV. To determine if the adoptive transfer of bi-specific CD8+ T cells eliminates CD19+ tumor cells in the subset of patients with a measurable tumor burden prior to T cell transfer.\n\nOUTLINE:\n\nAt least 30 days after HCT, patients will receive one intravenous (IV) infusion of CMV/CD19 or EBV/CD19 bi-specific CD8+ T cells.\n\nAfter completion of study treatment, patients are followed up periodically for 15 years.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:\n\n * Philadelphia chromosome negative acute lymphoblastic leukemia:\n\n * Beyond first complete remission (CR) at the time of pre-transplant evaluation\n * Required \\> 1 cycle of induction chemotherapy to achieve CR\n * First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)\n * First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or \\> 5 cytogenetic abnormalities) at diagnosis\n * Planned for or have had a reduced intensity conditioned or non-myeloablative transplant\n * Philadelphia positive acute lymphoblastic leukemia\n\n * Not in CR at the time of pre-transplant evaluation\n * In CR with the following features:\n\n * Intolerant or unwilling to use a TKI after HCT\n * Current or previous detection of cytogenetic abnormalities in addition to t(9;22) by conventional karyotyping, FISH or molecular methods\n * Chronic lymphocytic leukemia, or low grade B cell lymphomas:\n\n * Failed or ineligible for prior immunochemotherapy that included a purine analog and anti-CD20 monoclonal antibody AND a lymph node \\>= 5 cm at the time of pre-transplant evaluation\n * Mantle cell lymphoma:\n\n * Failed or ineligible for autologous transplant AND a lymph node \\>= 2 cm at the time of pre-transplant evaluation\n * Diffuse large B cell lymphomas, large B cell transformation of an indolent lymphoma or other aggressive B cell lymphomas\n\n * Failed or ineligible for autologous transplant AND not in CR at the time of pre-transplant evaluation\n* Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services\n* The patient has signed the informed consent form for this study\n* DONOR: Genotypic or phenotypic HLA-identical family members\n* DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:\n\n * CMV seropositive and HLA-A\\*0101 positive\n * CMV seropositive and HLA-A\\*0201 positive\n * CMV seropositive and HLA-B\\*0702 positive\n * CMV seropositive and HLA-B\\*0801 positive\n * EBV seropositive and HLA-A\\*0201 positive\n * EBV seropositive and HLA-B\\*0801 positive\n* DONOR: Hematocrit \\>= 35% at enrollment\n* DONOR: Age \\>= 18 years\n* DONOR: The donor has signed the informed consent form for the study\n\nExclusion Criteria:\n\n* Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible\n* Human immunodeficiency virus (HIV) seropositive\n* Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy\n* Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment\n* Pregnant or breast-feeding\n* DONOR: G-CSF administered within one month prior to the blood draw for T cell collection\n* DONOR: Unable for any reason to provide a 400 ml blood draw\n* DONOR: Inadequate peripheral veins for blood collection\n* DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive\n* DONOR: Active hepatitis B or hepatitis C virus infection\n* DONOR: Positive serologic test for syphilis\n* DONOR: Aberrant CD45RA isoform expression on all T cells\n* DONOR: Systolic blood pressure (BP) \\< 80 or \\> 200\n* DONOR: Heart rate \\< 50 or \\> 120, if considered due to cardiac disease\n* DONOR: Oxygen (O2) saturation \\< 88% on room air\n* DONOR: Serum creatinine (Cr) \\> 3.0\n* DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \\> 4 x the upper limit of normal\n* DONOR: Unable to provide informed consent to participate\n* DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors\n* DONOR: Pregnant or nursing'}, 'identificationModule': {'nctId': 'NCT01475058', 'briefTitle': 'CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant', 'organization': {'class': 'OTHER', 'fullName': 'Fred Hutchinson Cancer Center'}, 'officialTitle': 'A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-derived Virus-specific CD8+ T-cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant', 'orgStudyIdInfo': {'id': '2494.00'}, 'secondaryIdInfos': [{'id': 'NCI-2011-01819', 'type': 'REGISTRY', 'domain': 'CTRP (Clinical Trial Reporting Program)'}, {'id': '2494.00', 'type': 'OTHER', 'domain': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium'}, {'id': 'P30CA015704', 'link': 'https://reporter.nih.gov/quickSearch/P30CA015704', 'type': 'NIH'}, {'id': 'R01CA136551', 'link': 'https://reporter.nih.gov/quickSearch/R01CA136551', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (T cell therapy)', 'description': 'Patients undergo one IV infusion of donor-derived CD8+ central memory-derived CMV/CD19 or EBV/CD19 bi-specific T cells, at least 30 days after HCT.', 'interventionNames': ['Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes']}], 'interventions': [{'name': 'allogeneic cytomegalovirus-specific cytotoxic T lymphocytes', 'type': 'BIOLOGICAL', 'otherNames': ['allogeneic CMV-specific CTLs'], 'description': 'Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV', 'armGroupLabels': ['Treatment (T cell therapy)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '98109', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}], 'overallOfficials': [{'name': 'Cameron Turtle', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fred Hutchinson Cancer Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Cameron Turtle', 'investigatorAffiliation': 'Fred Hutchinson Cancer Center'}}}}