B7-H3 CAR-T for Recurrent or Refractory Glioblastoma

• Status: Recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.; Huizhou Municipal Central Hospital; Huzhou Central Hospital; Ningbo Yinzhou People's Hospital
• Treatments: Temozolomide

Criteria

Inclusion Criteria:

• 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 Criteria:

• 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)