Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma

March 2023:

Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: a “3+3” design is used to determine Maximum Tolerated Dose (MTD) and the recommended phase 2 dose (RP2D)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open, Single-arm, Phase 1 Study to Evaluate the Safety/Preliminary Effectiveness and Determine the Maximal Tolerated Dose of B7-H3-targeting CAR-T Cell Therapy in Treating Recurrent Glioblastomas
Actual Study Start Date : January 27, 2022
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

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.

Criteria

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.