Ignite Creation Date:
2025-12-24 @ 4:14 PM
Ignite Modification Date:
2025-12-27 @ 1:17 PM
Study NCT ID:
NCT04077866
Status:
UNKNOWN
Last Update Posted:
2022-12-28
First Post:
2019-08-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
B7-H3 CAR-T for Recurrent or Refractory Glioblastoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005909', 'term': 'Glioblastoma'}], 'ancestors': [{'id': 'D001254', 'term': 'Astrocytoma'}, {'id': 'D005910', 'term': 'Glioma'}, {'id': 'D018302', 'term': 'Neoplasms, Neuroepithelial'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077204', 'term': 'Temozolomide'}], 'ancestors': [{'id': 'D003606', 'term': 'Dacarbazine'}, {'id': 'D014226', 'term': 'Triazenes'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-06-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-12', 'completionDateStruct': {'date': '2025-08-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-12-25', 'studyFirstSubmitDate': '2019-08-26', 'studyFirstSubmitQcDate': '2019-09-03', 'lastUpdatePostDateStruct': {'date': '2022-12-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-09-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-06-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Cytokine levels in PB and CSF', 'timeFrame': '12 weeks', 'description': 'The concentration of cytokines (IL-1, IL-2, IL-6, IL-10, TNF-α, IFN-γ) in PB and CSF'}, {'measure': 'T cell levels and phenotype', 'timeFrame': '12 weeks', 'description': 'The chimeric antigen receptor (CAR) T and endogenous T cell levels and memory/effector phenotype detected in peripheral blood (PB), and cerebral spinal fluid (CSF) (absolute number per ul). Statistical and graphical methods will be used to describe persistence and expansion'}], 'primaryOutcomes': [{'measure': 'Overall survival (OS)', 'timeFrame': '2 years, up to 15 years if necessary', 'description': 'Kaplan Meier methods will be used to estimate median OS'}], 'secondaryOutcomes': [{'measure': 'Incidence and type of adverse events', 'timeFrame': '12 weeks', 'description': 'Number of Participants With Treatment-Related Adverse Events and Types of adverse events as Assessed by CTCAE v4.0'}, {'measure': 'Maximum tolerated dose (MTD)', 'timeFrame': '12 weeks', 'description': 'The highest dose of B7-H3 CAR-T that does not cause targeted dose-limiting toxicity'}, {'measure': 'Progression-free survival (PFS)', 'timeFrame': '2 years, up to 15 years if necessary', 'description': 'Kaplan Meier methods will be used to estimate median PFS. Progression is defined by Response Assessment in Neuro-Oncology (RANO) criteria'}, {'measure': 'Peak Concentration (Cmax) of B7-H3 CAR-T', 'timeFrame': '12 weeks', 'description': 'Peak Concentration (Cmax) of B7-H3 CAR-T in peripheral blood (PB) and cerebral spinal fluid (CSF)'}, {'measure': 'Area under the concentration versus time curve (AUC) of B7-H3 CAR-T', 'timeFrame': '12 weeks', 'description': 'Area under the concentration versus time curve (AUC) of B7-H3 CAR-T in peripheral blood (PB) and cerebral spinal fluid (CSF)'}, {'measure': 'Disease response (ORR, CR, PR, DOR)', 'timeFrame': '2 years, up to 15 years if necessary', 'description': 'Objective Response Rate (ORR) will be assessed by comparison with baseline magnetic resonance imaging by RANO. Complete Response (CR) is disappearance of all measurable and non-measurable disease for at least 4 weeks. Partial Response (PR) is \\>/= 50% decrease in lesions for at least 4 weeks. Duration of Response (DOR) is the time between the initial response to the treatment and subsequent disease progression.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Recurrent Glioblastoma', 'Refractory Glioblastoma']}, 'referencesModule': {'references': [{'pmid': '35468680', 'type': 'DERIVED', 'citation': 'Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.'}]}, 'descriptionModule': {'briefSummary': 'This is a randomized, parallel-arm, phase I/II study to evaluate the safety and efficacy of B7-H3 CAR-T in between Temozolomide cycles comparing to Temozolomide alone in treating patients with glioblastoma that has come back or does not respond to the standard treatment. The antigen B7-H3 is highly expressed in glioblastoma of a subset of patients. B7-H3 CAR-T, made from isolated patient peripheral blood mononuclear cells, can specifically attack patient glioblastoma cells that expressing B7-H3.', 'detailedDescription': 'Background\n\n* B7-H3 is expressed in 70% of patients with glioblastoma\n* B7-H3 is not expressed in normal tissues especially not in central nervous system. Therefore, it is an attractive GBM target for CAR-T therapy\n* The investigators constructed a retroviral vector encoding a chimeric antigen receptor (CAR) targeting B7-H3, which can mediate CAR transfer into patient T cells with high efficiency.\n\nObjectives\n\n* To evaluate the safety and tolerability intratumoral/intracerebroventricular injection of B7-H3 CAR-T when used in between Temozolomide cycles\n* To compare the overall survival (OS) and progression-free survival (PFS) of R/R GBM patients treated with B7-H3 CAR-T in between Temozolomide cycles vs Temozolomide alone\n* To access the pharmacokinetics and pharmacodynamics of B7-H3 CAR-T in between Temozolomide cycles\n\nDesign\n\n* Experimental group: Patients autologous T cells are activated and transduced with retrovirus containing B7-H3 CAR. CAR-T cells are expanded ex vivo and infused back to patients via intratumoral or intracerebroventricular injection through an Ommaya catheter. 3 injections of CAR-T are planned at two different doses with 1-2 weeks intervals. The CAR-T injections occur in between Temozolomide (TMZ) cycles. Temozolomide treatment during the cycles of CAR-T injections will be stopped and resumed next cycle. Patients may receive additional CAR-T cycles at the discretion of the principal investigator and oncologist.\n* Control group: Patients will receive regular cycles of Temozolomide treatment with 5 days of treatment and 23 days of interval.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Documented informed consent of the participant and/or legally authorized representative.\n* Histologically confirmed diagnosis of World Health Organization (WHO) classification grade IV glioblastoma (GBM).\n* Clinical Pathology confirms B7-H3 positive tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \\>= 50).\n* Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.\n* Suitable for the surgery of the placement of the Ommaya catheter.\n* Eastern Cooperative Oncology Group (ECOG) =0 or 1 (need to be confirmed before intratumoral or intracerebroventricular injection)\n* \\>= 8 weeks after completion of front-line radiation therapy\n* \\>= 6 weeks after completion of nitrourea chemotherapy\n* \\>= 14 days after completion of Temozolomide or other chemotherapy\n* 2 weeks of wash-out time after completion of targeted therapy with related adverse events (AE) on baseline (4 weeks for Bevacizumab). Patients with other chronic AEs are in the investigator's judgement\n* Blood cell count： White blood count (WBC) \\>= 2000/μL；Neutrophil count \\>= 1500/μL；Platelets \\>= 100 x 103/μL；Hemoglobin \\>= 9.0 g/dL\n* Serum Creatinine \\<= 1.5×ULN or Creatinine Clearance Rate (Cockcroft and Gault) \\> 30 mL/min/1.73 m2\n* Alanine Transaminase (ALT) \\<= 5×ULN and total bilirubin \\< 2.0mg/dL\n* Lung function: Oxygen (O2) saturation \\>= 92% on room air and \\< CTCAE grade 1 dyspnea\n* Heart function: Left ventricular ejection fraction (LVEF) \\>= 40% by multigated acquisition (MUGA) scan or echocardiogram\n* Normal coagulation function: prothrombin time (PT)，activated partial thromboplastin time (APTT) and international normalized ratio (INR)\n* Good blood vessel condition for leukapheresis\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity within one year after B7-H3 CAR-T infusion\n\nExclusion Criteria:\n\n* Other active malignancy in the past 2 years except non-melanoma skin cancer, completely surgical removed low grade tumor, post-therapeutic limited-stage prostate cancer, biopsy confirmed in situ cervical carcinoma, PAP test confirmed squamous intraepithelial lesions\n* Participant is undergoing or planning to take other anti-tumor therapies\n* Participant is systematic steroid-dependent, or is expecting to be treated with systematic steroid\n* Active immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection\n* Active infection from fungi, bacteria and/or viruses\n* Known history of the following cardiac diseases in the past 6 months: New York Heart Association (NYHA) defined grade III or IV heart failure, cardiac angioplasty, myocardial infarction, unstable angina and other clinically significant heart diseases\n* Known history and/or clinically evident central nerve system diseases: seizure, epileptic seizure, aphasia, paralysis, stroke, severe brain damage, dementia, Parkinson's Disease, cerebellar diseases, organic brain syndrome and psychiatric disorders\n* Autoimmune diseases\n* Pregnant or breastfeeding females\n* Therapeutic doses of corticosteroid within 7 days before leukapheresis or 72 hours before B7-H3 CAR-T infusion\n* Cytotoxic chemotherapy without lymphocytotoxicity within 1 week before leukapheresis except that the treatment has been stopped for more than 3 half-lives of the drug\n* Lymphocytotoxic chemotherapy (cyclophosphamide, Ifosfamide and bendamustine) within 2 weeks before leukapheresis\n* Other clinical trials drugs within 4 weeks before leukapheresis except that the drug has no effect or the disease has progressed, and the treatment has been stopped for more than 3 half-lives of the drug\n* Radiotherapy within 6 weeks before leukapheresis\n* Prior trials of CAR-T or other cell therapy\n* Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)"}, 'identificationModule': {'nctId': 'NCT04077866', 'briefTitle': 'B7-H3 CAR-T for Recurrent or Refractory Glioblastoma', 'organization': {'class': 'OTHER', 'fullName': 'Second Affiliated Hospital, School of Medicine, Zhejiang University'}, 'officialTitle': 'B7-H3-Targeted Chimeric Antigen Receptor (CAR) T Cells in Treating Patients With Recurrent or Refractory Glioblastoma', 'orgStudyIdInfo': {'id': 'SAHZJU-RCT-BP102'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Temozolomide alone', 'description': 'Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped.', 'interventionNames': ['Drug: Temozolomide']}, {'type': 'EXPERIMENTAL', 'label': 'Temozolomide + B7-H3 CAR-T', 'description': 'Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped.\n\nThe B7-H3 CAR-T will be administrated via intratumoral or Intracerebroventricular injection through an Ommaya catheter in between Temozolomide cycles. Temozolomide treatment in the cycles of B7-H3 CAR-T treatment will be stopped.', 'interventionNames': ['Drug: Temozolomide', 'Biological: B7-H3 CAR-T']}], 'interventions': [{'name': 'Temozolomide', 'type': 'DRUG', 'otherNames': ['TMZ'], 'description': 'Temozolomide is an FDA-approved drug that is given to patients', 'armGroupLabels': ['Temozolomide + B7-H3 CAR-T', 'Temozolomide alone']}, {'name': 'B7-H3 CAR-T', 'type': 'BIOLOGICAL', 'description': 'B7-H3-targeting CAR-T cells derived from patient own peripheral blood mononuclear cells will be given to patients via intracerebral injection though an Ommaya catheter', 'armGroupLabels': ['Temozolomide + B7-H3 CAR-T']}]}, 'contactsLocationsModule': {'locations': [{'zip': '310009', 'city': 'Hangzhou', 'state': 'Zhejiang', 'status': 'RECRUITING', 'country': 'China', 'contacts': [{'name': 'Jianmin Zhang, MD', 'role': 'CONTACT', 'email': '2307010@zju.edu.cn', 'phone': '86-13805722695'}], 'facility': 'the Second Affiliated Hospital of Zhejiang University School of Medicine', 'geoPoint': {'lat': 30.29365, 'lon': 120.16142}}, {'zip': '313003', 'city': 'Huzhou', 'state': 'Zhejiang', 'status': 'NOT_YET_RECRUITING', 'country': 'China', 'contacts': [{'name': 'Zhongzhou Su, MD', 'role': 'CONTACT'}], 'facility': 'Huzhou Central Hospital', 'geoPoint': {'lat': 30.8703, 'lon': 120.0933}}, {'zip': '315040', 'city': 'Ningbo', 'state': 'Zhejiang', 'status': 'NOT_YET_RECRUITING', 'country': 'China', 'contacts': [{'name': 'Feng Gao, MD', 'role': 'CONTACT'}], 'facility': "Ningbo Yinzhou People's Hospital", 'geoPoint': {'lat': 29.87819, 'lon': 121.54945}}], 'centralContacts': [{'name': 'Jianmin Zhang, MD', 'role': 'CONTACT', 'email': '2307010@zju.edu.cn', 'phone': '+86-13805722695'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Second Affiliated Hospital, School of Medicine, Zhejiang University', 'class': 'OTHER'}, 'collaborators': [{'name': "Ningbo Yinzhou People's Hospital", 'class': 'UNKNOWN'}, {'name': 'Huizhou Municipal Central Hospital', 'class': 'OTHER'}, {'name': 'BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}