Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therap... | NCT05241392

NCT05241392

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CAR-T cell therapy	Experimental	Dose-escalation phase: A "3+3" dose-escalation design is used to determine MTD & R2PD. Anti-B7-H3 autologous CAR-T cells were given biweekly to patients at the following doses for each cycle, and 4 cycles as one course. Dose1: 3 patients at a dose of 20 million cells for each cycle. Dose 2: 3 patients at a dose of 60 million cells for each cycle. Dose 3: 3 patients at a dose of 150 million cells for each cycle. Dose 4: 3 patients at a dose of 450 million cells for each cycle. Dose 5: 3 patients at a dose of 900 million cells for each cycle. R2PD confirmation phase: Determine the R2PD based on the results from the previous dose-escalation study; Treat another 12 patients with anti-B7-H3 autologous CAR-T cells biweekly at the R2PD to further confirm the safety of R2PD. At each dose phase, if the patients show tolerate and response to the treatment, these patients would receive several courses of treatment at PI's discretion.	Biological: B7-H3-targeting CAR-T cells

Interventions

Name	Type	Description	Arm Group Labels	Other Names
B7-H3-targeting CAR-T cells	Biological	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of Dose Limiting Toxicity (DLT)	To evaluate the DLT incidence occurred within three months after B7-H3 CAR-T cells infusion	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	three months post CAR-T cells infusion

Secondary Outcomes

Measure	Description	Time Frame
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	12 months post CAR-T cells infusion
Efficacy：objective remission rate

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, aged 18-75 years (including 18 and 75 years old)；
Patients with relapsed glioblastoma, as confirmed by positron emission tomography (PET) or histologic pathology；
A >= 30% staining extent of B7-H3 in his/her primary/recurrent tumor tissue by the immunochemical method;
Karnofsky scale score>=50
Availability in collecting peripheral blood mononuclear cells (PBMCs) ；
Adequate laboratory values and adequate organ function;
Patients with childbearing/fathering potential must agree to use highly effective contraception；

Exclusion Criteria:

Pregnant or breastfeeding females；
Contraindication to bevacizumab；
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)；
Comorbid with Other uncontrolled malignancy；
Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection;
Subjects receiving the placement of a carmustine slow-release wafer within 6 months before the enrollment;
Autoimmune diseases;
Receiving long-term immunosuppressive treatment after organ transplantation;
Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes;
Not recovered from the toxicities or side effects by previous treatment;
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.
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
Subjects with other conditions that would interfere trial participation at the investigator's discretion.

ID	Term
D001254	Astrocytoma
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors