B7-H3 CAR-T treatment for recurrent glioblastoma

B7-H3-Targeted Chimeric Antigen Receptor (CAR) T Cells in Treating Patients With Recurrent or Refractory Glioblastoma

This study is testing a new CAR-T therapy for people with recurrent glioblastoma to see if it works better than the standard treatment with Temozolomide.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: Bevacizumab, CAR-T, chemotherapy, radiation, cyclophosphamide, chimeric antigen receptor
• Locations: 3 sites (Hangzhou, Zhejiang and 2 other locations)
• Trial ID: NCT04077866 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of B7-H3 CAR-T therapy in patients with recurrent or refractory glioblastoma, comparing it to standard treatment with Temozolomide. The approach involves using a retroviral vector to modify patients' T cells to target the B7-H3 antigen, which is highly expressed in glioblastoma cells. Patients will receive intratumoral or intracerebroventricular injections of CAR-T cells during breaks in their Temozolomide treatment. The study aims to assess overall survival and progression-free survival rates, as well as the pharmacokinetics and pharmacodynamics of the CAR-T therapy.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed grade IV glioblastoma that expresses the B7-H3 antigen and have relapsed or refractory disease.

Not a fit: Patients with glioblastoma that does not express the B7-H3 antigen or those who are not suitable for the placement of an Ommaya catheter may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new, targeted therapy option for patients with glioblastoma that is resistant to standard treatments.

How similar studies have performed: Other studies have shown promise with CAR-T therapies targeting different antigens, but this specific approach targeting B7-H3 in glioblastoma is relatively novel.

Eligibility 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)

Where this trial is running

Hangzhou, Zhejiang and 2 other locations

• the Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• Huzhou Central Hospital — Huzhou, Zhejiang, China (Not_yet_recruiting)
• Ningbo Yinzhou People's Hospital — Ningbo, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Jianmin Zhang, MD

Conditions Recurrent Glioblastoma; Refractory Glioblastoma