Clinical trial NCT06018363: Clinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection
Official title: Allogenic B7H3-targeting CAR-γδT Cell Therapy in r/r GBM
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Brain Gliomas
Keywords: B7H3
CAR-γδT
GBM
Lead sponsor: Dushu Lake Hospital Affiliated to Soochow University
Sponsor class: OTHER
First posted: 2023-08-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study on the clinical application of chimeric antigen receptor modified γδ T cells (CAR-γδ T cells) in relapsed and refractory B7H3 Positive malignant brain glioma.The main purpose of this study was to evaluate the safety and feasibility of CAR-γδ T cell infusion in patients with relapsed and refractory B7H3 Positive malignant brain glioma.

Detailed description: γδT cells are known as "a great candidate for car-t cells". Although they only account for 2% - 5% of all T cells in our body, they are a natural killer.

Treatment on this study includes six B7H3 CAR-γδ Tcell infusions over an 12 week period. B7H3 CAR-γδ T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety, feasibility and maximum tolerated dose (MTD) of B7H3 CAR-γδ T cell using a 3+3 study design and an 4 week evaluation period. The total study duration will be 2 years.

Eligibility criteria: Inclusion Criteria:

* 1)Age 18-70 years old (both ends included), both male and female;
* 2)At least one evaluable lesion with previous biopsy or pathohistologic confirmation of high-grade glioma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment;
* 3) Surgically resected pathological tissue capable of being used for immunohistochemical detection of target proteins and positive for B7H3 expression;
* 4) KPS ≥ 60 points;
* 5)Expected survival \> 3 months;
* 6)Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before receiving QH104 Cell Injection for the first time):White blood cell count (WBC) ≥ 3 x 109/L;Lymphocyte count (LY) ≥ 0.8 x 109/L;Hemoglobin (Hb) ≥ 90g/L;Platelet (PLT) ≥80×109/L;Albumin transaminase (ALT) \& albumin transaminase (AST) \<1.5×ULN;Serum creatinine (Cr) \<1.5 x ULN;Total bilirubin \< 1.5 x ULN;PT \& PTT ≤ 1.25 x ULN.
* 7)No obvious hereditary diseases;
* 8)Normal cardiac function with cardiac ejection index \>55%;
* 9)No bleeding and coagulation disorders;
* 10)Women of childbearing age (15-49 years old) must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception during the clinical trial and for 3 months after the last cell infusion;
* 11) Sign the informed consent form.

Exclusion Criteria:

* 1)Pregnant and lactating women;
* 2)Those with organ failure:Heart: Class III and IV;Liver: up to grade C of the Child-Turcotte Liver -Function Classification;Kidney: chronic kidney disease stage 4 or above; renal insufficiency stage III or above;Lungs: symptoms of severe respiratory failure with involvement of other organs;Brain: central nervous system abnormalities or impaired consciousness;
* 3)patients with combined second tumors;
* 4)patients with active hepatitis B or C virus, HIV infection, or other untreated active infection;
* 5)any severe, uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis;
* 6)Current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances;
* 7) have a chronic disease requiring immunologic or hormonal therapy;
* 8) have an allergy to immunotherapy and related cells;
* 9) 10)Patients with a history of organ transplantation or who are awaiting organ transplantation;
* 10)Participation in other clinical trials within the previous 30 days;
* 11)Those who are not suitable for clinical trials for other reasons in the opinion of the investigator.

Primary outcomes:
measure: Phase 1: Incidence of Adverse Events (AEs)
timeFrame: 12 months
measure: Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)
timeFrame: First infusion date of B7H3 CAR-γδT cells up to 28 days
measure: Phase 1:Maximum tolerated dose (MTD)
timeFrame: First infusion date of B7H3 CAR-γδT cells up to 28 days
measure: Phase 1: Recommended phase 2 dose (RP2D)
timeFrame: First infusion date of B7H3 CAR-γδT cells up to 28 days
measure: Phase 2: Best objective Response Rate
timeFrame: 12 months
Secondary outcomes:
measure: Phase 2: Overall Survival (OS)
timeFrame: 12 months
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: 12 months
measure: Pharmacokinetics: Number and copy number of B7H3 CAR-γδT cells (phase 1 and phase 2)
timeFrame: First infusion date of B7H3 CAR-γδT cells up to 28 days
measure: Pharmacodynamics: Peak level of cytokines in CSF (phase 1 and phase 2)
timeFrame: First infusion date of B7H3 CAR-γδT cells up to 28 days
Other outcomes:
Locations:
city: Suzhou
country: China
facility: Dushu Lake Hospital Affiliated to Soochow University
state: Jiangsu
Study officials:
References: