Clinical trial NCT05241392: Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Glioblastoma
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2022-02-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: a "3+3" design is used to determine Maximum Tolerated Dose (MTD) and the recommended phase 2 dose (RP2D)
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicity (DLT)
timeFrame: three months post CAR-T cells infusion
measure: Safety：Incidence and severity of adverse events
timeFrame: three months post CAR-T cells infusion
Secondary outcomes:
measure: Efficacy：Overall survival rate at 12 months
timeFrame: 12 months post CAR-T cells infusion
measure: Efficacy：objective remission rate
timeFrame: 1, 2, 3, 4, 5, 6 months post CAR-T cells infusion
measure: pharmacokinetics：Cmax
timeFrame: 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
measure: pharmacokinetics：Tmax
timeFrame: 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
measure: pharmacokinetics：AUC
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Nan Ji, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.