Tris-CAR-T Cell Therapy for Recurrent Glioblastoma

Phase 1 Study of Autologous Tris-CAR-T Cell Locoregional Immunotherapy for Recurrent Glioblastoma

This study is testing a new treatment using modified immune cells to see if it helps people with recurring glioblastoma feel better and fight their cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Drugs / interventions: bevacizumab, CAR-T, immunotherapy, radiation, chimeric antigen receptor
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05577091 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a novel Tris-CAR-T cell therapy targeting recurrent glioblastoma. Patients will undergo leukapheresis to collect T cells, which will then be genetically modified to express a dual-target chimeric antigen receptor. The modified T cells will be infused into patients via an Ommaya reservoir placed in the tumor resection cavity. The trial will monitor patient responses and side effects over multiple doses.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a confirmed diagnosis of recurrent glioblastoma and residual tumor after surgery.

Not a fit: Patients with significant comorbidities or those who have not completed prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with recurrent glioblastoma, potentially improving survival rates.

How similar studies have performed: Previous studies on CAR-T cell therapies have shown promising results, indicating potential for success with this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Age: 18 years to 70 years (including cut-off values).
2. Patients with history of glioblastoma are diagnosed with recurrent glioblastoma and residual tumor after intracranial tumor resection/biopsy performed in Beijing Tiantan Hospital.
3. Patients who finished radiotherapy or temozolomide/bevacizumab or other drugs for at least 4 weeks. All toxicities of prior treatment should be defined as less than or equal to grade 1 (except for toxicities such as hair loss or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 5.0).
4. Patients who is suitable for craniotocerebrospinal fluid shunt and attachment (Ommaya device) implantation confirmed by a competent physician.
5. Patients and/or legal representative is able to sign written informed consent.
6. Kanovsky Performance Status (KPS) ≥ 70.
7. According to the researchers' judgment, the life expectancy ≥ 8 weeks.
8. White blood cells (WBC) \> 3.50×10\^9/L (performed within 14 days prior to PBMC collection unless otherwise noted).
9. Platelet ≥ 200×10\^9/L (performed within 14 days prior to PBMC collection unless otherwise noted).
10. Hemoglobin ≥ 120 g/L (performed within 14 days prior to PBMC collection unless otherwise noted).
11. Total bilirubin ≤ 20 μmol/L (performed within 14 days prior to PBMC collection unless otherwise noted).
12. Aspartic acid aminotransferase (AST) ≤ 2.5×42 U/L (performed within 14 days prior to PBMC collection unless otherwise noted).
13. Alanine aminotransferase (ALT) ≤ 2.5×41 U/L (performed within 14 days prior to PBMC collection unless otherwise noted).
14. Serum creatinine ≤ 90 μmol/L (performed within 14 days prior to PBMC collection unless otherwise noted).
15. Blood oxygen saturation ≥ 95% (performed within 14 days prior to PBMC collection unless otherwise noted).
16. Seronegative of the combination of human immunodeficiency virus (HIV) antibody (Ab) (performed within 14 days prior to PBMC collection unless otherwise noted).
17. Fertile women: a negative serum pregnancy test (performed within 14 days prior to PBMC collection unless otherwise noted).
18. The patient agrees that contraception should be used in patients of childbearing age for at least 3 months from screening to the last infusion of Tris-CAR-T cells. The period of childbearing age is defined as unsurgically neutered (men and women) or without menopause for more than 1 year (women only).

Exclusion Criteria:

1. Kanovsky Performance Status (KPS) ≤ 70.
2. Highly allergic constitution or severe allergies history.
3. Those who have psychiatric or psychological diseases and cannot cooperate with treatment and efficacy assessment.
4. Receive other drug trials within 60 days before enrollment, or receive other routine treatment in non-experimental designs for glioblastoma, such as stereotactic radiation therapy or placement of carmustine wafers.
5. Combined with infection, active infection, fever of unknown cause.
6. Combined with serious or unstable heart, lung, liver, kidney and hematopoietic system diseases, including active hepatitis.
7. Combined with inflammation and immune system diseases (such as rheumatoid arthritis), or known immunosuppressive diseases.
8. Combined with neurological diseases, such as diffuse leptomeningeal disease, or neurodegenerative diseases.
9. Known allergies to immunotherapy and related cellular products.
10. Patients who have received any gene therapy before.
11. Long-term use of immunosuppressants is required for any reason.
12. Patients with a history of organ transplantation or who are waiting for organ transplantation.
13. Special cases: pregnancy or lactation.
14. Other circumstances in which the investigators believe the patient is unsuitable for this trial.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Tiantan Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Wei Zhang, Prof.

Conditions Recurrent Glioblastoma; Immunotherapy; Adverse Events