Ignite Creation Date:
2025-12-25 @ 3:53 AM
Ignite Modification Date:
2025-12-26 @ 2:42 AM
Study NCT ID:
NCT06252402
Status:
RECRUITING
Last Update Posted:
2025-02-18
First Post:
2024-02-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/AIDS
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 15}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-12-19', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-02', 'completionDateStruct': {'date': '2026-12-11', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-02-17', 'studyFirstSubmitDate': '2024-02-01', 'studyFirstSubmitQcDate': '2024-02-01', 'lastUpdatePostDateStruct': {'date': '2025-02-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-02-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12-11', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Dose limiting toxicities (DLT)', 'timeFrame': 'Up to 28 days after the infusion', 'description': 'Toxicity will be graded per CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria on CRS/Neurotoxicity: DLT.'}, {'measure': 'Toxicity profile', 'timeFrame': 'Up to 28 days after the infusion', 'description': 'Toxicity will be graded per CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria on CRS/Neurotoxicity: all other toxicities to define the toxicity profile.'}], 'secondaryOutcomes': [{'measure': 'CD4+ T cell count and HIV RNA levels', 'timeFrame': 'Up to 28 days after the infusion', 'description': 'CD4+ T cell count and HIV RNA levels in the peripheral blood;'}, {'measure': 'EGFR+ CD3+ T cells', 'timeFrame': 'Up to 28 days after the infusion', 'description': 'Number, percentage and persistence of EGFR+ CD3+ T cells in the peripheral blood and EGFR- CD3+ T cells in peripheral blood'}, {'measure': 'Cytokine levels', 'timeFrame': 'Up to 28 days after the infusion', 'description': 'Cytokine levels in the peripheral blood post CAR T cell infusion.'}, {'measure': 'Number of CMV/HIV-CAR T cells', 'timeFrame': 'Up to 28 days after the infusion', 'description': 'Number of CMV/HIV-CAR T cells: measured by qPCR in peripheral blood); and Using two in-depth interviews (1) shortly following screening (within 2 weeks), and 2) within 1 month of initiating Step 4, we will assess perceptions of the CMV/HIV-CAR T cell intervention and overall trial experiences in participants'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['HIV-1, PLWH (Healthy People Living with HIV-1) autologus', 'CMV-specific T cells, anti-retroviral therapy (ART), Immunotherapy'], 'conditions': ['HIV-1']}, 'descriptionModule': {'briefSummary': 'Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIVCAR T cells) may provide a safe and effective way to eliminate HIV-infected cells.\n\nHowever, the number of HIV-infected cells is low in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of HIV-1-infected individuals are CMV-seropositive and CMV-specific T cells have been shown to persist. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human Phase 1, open-label, single-arm study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH), and achieve long-term remission in the presence of ART.', 'detailedDescription': 'Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIV-CAR T cells) may provide a safe and effective way to eliminate HIV-infected cells. However, HIV-infected cells in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of individuals with HIV-1 are CMV-seropositive and CMV-specific T cells have been shown to persist at high frequency due to CMV antigen stimulation. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human, open-label, single-arm, pilot study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH). Based on the results of this safety study, CMV vaccine and analytic treatment interruption will be evaluated with the CMV/HIV-CAR T cell investigational product in a subsequent protocol.\n\nThe trial is a first-in-human, pilot study to evaluate the feasibility and safety and determine the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of CMV/HIV-CAR T cells in PLWH. Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cell manufacturing. Participants will resume their ART regimen immediately after leukapheresis. If the manufacturing is not successful, a second apheresis may be scheduled no sooner than 3 weeks later with temporary interruption of ART regimen for 4 days prior to leukapheresis. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV) infusion of autologous CMV/HIV-CAR T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cells may be explored.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Participant must be ≥ 18 years of age at the time of screening;\n* Karnofsky Performance Status (KPS) ≥ 70;\n* Documented HIV-1 infection anytime prior to study entry.;\n* On stable ART with undetectable HIV-1 RNA (i.e \\< 20 copies /mL) for at least 48 weeks prior to screening (2 plasma HIV-1 RNA blips 25-200 copies/mL are allowable);\n* CD4+ cell count ≥ 450 cells/μL;\n* Adequate organ function;\n* Willingness to interrupt ART regimen for 4 days prior to leukapheresis;\n* Not pregnant or breastfeeding.\n\nExclusion Criteria:\n\n* Concurrent illness or comorbid condition;\n* History of resistance to two or more classes of antiretroviral drugs;\n* History of prior receipt of an experimental HIV-1, immunotherapeutic agent, or gene therapy product.'}, 'identificationModule': {'nctId': 'NCT06252402', 'briefTitle': 'CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/AIDS', 'organization': {'class': 'OTHER', 'fullName': 'City of Hope Medical Center'}, 'officialTitle': 'A Pilot Study to Evaluate the Feasibility and Safety of Cytomegalovirus-Specific, Anti-HIV Chimeric Antigen Receptor (CMV-HIV CAR) T Cells in People Living With HIV', 'orgStudyIdInfo': {'id': '22508'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dose Level -1', 'description': 'EGFR+ T Cell Dose (Day 0) 5 x 10\\^6 cells', 'interventionNames': ['Biological: CMV/HIV-CAR T Cells']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Level +1', 'description': 'EGFR+ T Cell Dose (Day 0) 25 x 10\\^6 cells', 'interventionNames': ['Biological: CMV/HIV-CAR T Cells']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Level +2', 'description': 'EGFR+ T Cell Dose (Day 0) 50 x 10\\^6 cells', 'interventionNames': ['Biological: CMV/HIV-CAR T Cells']}], 'interventions': [{'name': 'CMV/HIV-CAR T Cells', 'type': 'BIOLOGICAL', 'description': 'Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cewll manufacturing. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV)infusion of autologous CMV/HIV-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.', 'armGroupLabels': ['Dose Level +1', 'Dose Level +2', 'Dose Level -1']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91010', 'city': 'Duarte', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'John H. Baird, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'City of Hope Medical Center', 'geoPoint': {'lat': 34.13945, 'lon': -117.97729}}, {'zip': '92093', 'city': 'San Diego', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'David Smith, MD', 'role': 'CONTACT'}, {'name': 'David Smith, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'UCSD, Division of Infectious Diseases and Global Public Health', 'geoPoint': {'lat': 32.71571, 'lon': -117.16472}}], 'centralContacts': [{'name': 'Marvin Hanashiro', 'role': 'CONTACT', 'email': 'mhanashiro@health.ucsd.edu', 'phone': '(619) 543-3740'}, {'name': 'Steven Hendrickx', 'role': 'CONTACT', 'email': 'smhendrickx@health.ucsd.edu', 'phone': '(619) 543-6968'}], 'overallOfficials': [{'name': 'John H. Baird, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'City of Hope Medical Center'}, {'name': 'David (Davey) Smith, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'UCSD, San Diego Center for AIDS Research'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'City of Hope Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}