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

Glioblastoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05241392
• Other study ID #: TX103T-IG005
• Status: Recruiting
• Phase: Phase 1
• Start date: January 27, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Beijing Tiantan Hospital
• Contact: Yang T Zhang, Dr.
• Phone: +861059976516
• Email: zhangyang8025[@]yeah.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Biological:
• B7-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.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Efficacy:objective remission rate	The proportion of subjects reaching complete remission / partial remission in optimal remission	1, 2, 3, 4, 5, 6 months post CAR-T cells infusion
Secondary	pharmacokinetics:Cmax	observed maximum plasma concentration (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
Secondary	pharmacokinetics:Tmax	time to reach maximum plasma concentration (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
Secondary	pharmacokinetics:AUC	area under the plasma concentration-time curve from time zero to 28 days after dosing (AUC(0-28))	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