Active, not recruiting
Phase 1
Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma
Condition(s) studied
Glioblastoma
Investigational drug(s) / intervention(s)
B7-H3-targeting CAR-T cells/TX103-CAR-T Cell Injection
B7-H3-targeting CAR-T cells/TX103-CAR-T Cell Injection: Patients will be treated with anti-B7-H3 autologous CAR-T cells that are delivered into the intracranial tumor resection cavity or ventricular system using an Ommaya device.
Study summary
This is an open-label, single-arm, dose-escalation and multiple-dose study to evaluate the safety, tolerability, and preliminary efficacy of TX103-CAR-T Cell Injection, a B7-H3-targeting chimeric antigen receptor T-cell (CAR-T) therapy, in patients with recurrent glioblastoma. The study also aims to explore the maximum tolerated dose (MTD) and determine the recommended Phase II dose (RP2D) of TX103-CAR-T Cell Injection.
Eligibility
Inclusion Criteria:
1. Male or female, aged 18-75 years (including 18 and 75 years old);
2. Patients with relapsed glioblastoma, as confirmed by positron emission tomography (PET) or histologic pathology;
3. A \>= 30% staining extent of B7-H3 in his/her primary/recurrent tumor tissue by the immunochemical method;
4. Karnofsky scale score\>=50
5. Availability in collecting peripheral blood mononuclear cells (PBMCs) ;
6. Adequate laboratory values and adequate organ function;
7. Patients with childbearing/fathering potential must agree to use highly effective contraception;
Exclusion Criteria:
1. Pregnant or breastfeeding females;
2. Contraindication to bevacizumab;
3. Within 5 days before the CAR-T cell infusion, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids ( not including inhaled corticosteroid);
4. Comorbid with Other uncontrolled malignancy;
5. Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection;
6. Subjects receiving the placement of a carmustine slow-release wafer within 6 months before the enrollment;
7. Autoimmune diseases;
8. Receiving long-term immunosuppressive treatment after organ transplantation;
9. Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes;
10. Not recovered from the toxicities or side effects by previous treatment;
11. Subjects who have participated the other interventional trial within one month before the enrollment, or have received other CAR-T cell therapies or gene-modified cell therapy before enrollment.
12. Subjects with medical conditions that affect signing the written informed consent or complying with the research procedures, the medical conditions including, but not limited to cardio-cerebral vascular diseases, renal dysfunction/failure, pulmonary embolism, coagulation disorders, active systemic infection, uncontrolled infection et. al; or patients who are unwilling or unable to comply with the research procedures; these
13. Subjects with other conditions that would interfere trial participation at the investigator's discretion.
Primary outcome measure(s)
- Incidence of Dose Limiting Toxicity (DLT) — three months post CAR-T cells infusion
To evaluate the DLT incidence occurred within three months after B7-H3 CAR-T cells infusion
- Safety:Incidence and severity of adverse events — three months post CAR-T cells infusion
To evaluate the possible adverse events occurred within three months after B7-H3 CAR-T cell infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity
Trial sites (1)
| Facility | City | Region | Status |
| Beijing Tiantan Hospital |
Beijing |
Beijing Municipality |
|
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