Overview

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)