Glioblastoma
Conditions
Brief summary
This is an open, single-arm, dose-escalation and multiple-dose study to evaluate the safety, tolerability and preliminary effectiveness of B7-H3-targeting Chimeric Antigen Receptor-T (CAR-T) cell therapy on patients with recurrent glioblastomas. The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.
Interventions
BIOLOGICALB7-H3-targeting CAR-T cells
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.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
a "3+3" design is used to determine Maximum Tolerated Dose (MTD) and the recommended phase 2 dose (RP2D)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy：Overall survival rate at 12 months | 12 months post CAR-T cells infusion | The proportion of subjects who have survived for more than 12 months since the diagnosis of recurrent glioblastoma |
| Efficacy：objective remission rate | 1, 2, 3, 4, 5, 6 months post CAR-T cells infusion | The proportion of subjects reaching complete remission / partial remission in optimal remission |
| pharmacokinetics：Cmax | Samples collected pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Samples collected pre-injection, and 2, 7, 13 days post re-injections | observed maximum plasma concentration (Cmax) |
| pharmacokinetics：Tmax | Samples collected pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Samples collected pre-injection, and 2, 7, 13 days post re-injections | time to reach maximum plasma concentration (tmax) |
| pharmacokinetics：AUC | Sample taken pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Sample taken pre-injection, and 2,7,13 days post re-injections | area under the plasma concentration-time curve from time zero to 28 days after dosing (AUC(0-28)) |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORNan Ji, Dr.
Beijing Tiantan Hospital
Outcome results
None listed