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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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.
Beijing Tiantan Hospital
Beijing, Beijing Municipality, China
Incidence of Dose Limiting Toxicity (DLT)
To evaluate the DLT incidence occurred within three months after B7-H3 CAR-T cells infusion
Time frame: three months post CAR-T cells infusion
Safety:Incidence and severity of adverse events
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
Time frame: three months post CAR-T cells infusion
Efficacy:Overall survival rate at 12 months
The proportion of subjects who have survived for more than 12 months since the diagnosis of recurrent glioblastoma
Time frame: 12 months post CAR-T cells infusion
Efficacy:objective remission rate
The proportion of subjects reaching complete remission / partial remission in optimal remission
Time frame: 1, 2, 3, 4, 5, 6 months post CAR-T cells infusion
pharmacokinetics:Cmax
observed maximum plasma concentration (Cmax)
Time frame: 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
pharmacokinetics:Tmax
time to reach maximum plasma concentration (tmax)
Time frame: 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
pharmacokinetics:AUC
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area under the plasma concentration-time curve from time zero to 28 days after dosing (AUC(0-28))
Time frame: 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