Status:
UNKNOWN
B7-H3 CAR-T for Recurrent or Refractory Glioblastoma
Lead Sponsor:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborating Sponsors:
Ningbo Yinzhou People's Hospital
Huizhou Municipal Central Hospital
Conditions:
Recurrent Glioblastoma
Refractory Glioblastoma
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
PHASE2
Brief Summary
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 gliobla...
Detailed Description
Background * B7-H3 is expressed in 70% of patients with glioblastoma * B7-H3 is not expressed in normal tissues especially not in central nervous system. Therefore, it is an attractive GBM target for...
Eligibility Criteria
Inclusion
- Documented informed consent of the participant and/or legally authorized representative.
- Histologically confirmed diagnosis of World Health Organization (WHO) classification grade IV glioblastoma (GBM).
- Clinical Pathology confirms B7-H3 positive tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50).
- Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.
- Suitable for the surgery of the placement of the Ommaya catheter.
- Eastern Cooperative Oncology Group (ECOG) =0 or 1 (need to be confirmed before intratumoral or intracerebroventricular injection)
- \>= 8 weeks after completion of front-line radiation therapy
- \>= 6 weeks after completion of nitrourea chemotherapy
- \>= 14 days after completion of Temozolomide or other chemotherapy
- 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
- Blood cell count： White blood count (WBC) \>= 2000/μL；Neutrophil count \>= 1500/μL；Platelets \>= 100 x 103/μL；Hemoglobin \>= 9.0 g/dL
- Serum Creatinine \<= 1.5×ULN or Creatinine Clearance Rate (Cockcroft and Gault) \> 30 mL/min/1.73 m2
- Alanine Transaminase (ALT) \<= 5×ULN and total bilirubin \< 2.0mg/dL
- Lung function: Oxygen (O2) saturation \>= 92% on room air and \< CTCAE grade 1 dyspnea
- Heart function: Left ventricular ejection fraction (LVEF) \>= 40% by multigated acquisition (MUGA) scan or echocardiogram
- Normal coagulation function: prothrombin time (PT)，activated partial thromboplastin time (APTT) and international normalized ratio (INR)
- Good blood vessel condition for leukapheresis
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- 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
Exclusion
- 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
- Participant is undergoing or planning to take other anti-tumor therapies
- Participant is systematic steroid-dependent, or is expecting to be treated with systematic steroid
- Active immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection
- Active infection from fungi, bacteria and/or viruses
- 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
- 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
- Autoimmune diseases
- Pregnant or breastfeeding females
- Therapeutic doses of corticosteroid within 7 days before leukapheresis or 72 hours before B7-H3 CAR-T infusion
- 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
- Lymphocytotoxic chemotherapy (cyclophosphamide, Ifosfamide and bendamustine) within 2 weeks before leukapheresis
- 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
- Radiotherapy within 6 weeks before leukapheresis
- Prior trials of CAR-T or other cell therapy
- 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
- 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)
Key Trial Info
Start Date :
June 1 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 1 2025
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT04077866
Start Date
June 1 2023
End Date
August 1 2025
Last Update
December 28 2022
Active Locations (3)
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1
the Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China, 310009
2
Huzhou Central Hospital
Huzhou, Zhejiang, China, 313003
3
Ningbo Yinzhou People's Hospital
Ningbo, Zhejiang, China, 315040