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This is an open, single-arm, single-center, interventional clinical study. It is planned to enroll 3-6 patients with meningeal metastases from B7H3+ solid tumors and to explore, on a small scale, the efficacy of local injection of allogeneic B7H3 CAR-γδ T cells (3*107/dose) for the treatment of patients with meningeal metastases from B7H3+ solid tumors.
This study is an open, single-arm, single-center, interventional clinical study. It is planned to enroll 3-6 patients with meningeal metastases from B7H3+ solid tumors and to explore, on a small scale, the clinical response to local injection of allogeneic B7H3 CAR-γδ T cells (3*107/dose) for the treatment of patients with meningeal metastases from B7H3+ solid tumors. During the period of cell therapy, the enrolled subjects may be given additional multiple infusions of cells, after imaging, neurological function, cerebrospinal fluid cytology or the investigator's assessment of the potential benefit of continuing cell therapy. It is recommended that the frequency of multiple infusions be 2 weeks each, and the interval between infusions can be adjusted at a later stage based on the PK and clinical symptoms of the subject after infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| QH104 cell Injection(Allogenic B7H3 CAR-γδT cell) | Experimental | Plan to enroll 3 to 6 patients with meningeal metastasis of B7H3+ solid tumor with single or multiple local injections of allogenic B7H3 CAR-γδ T cells (3*107/ dose) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QH104 Cell injection | Biological | Patients will first be pre-screened for B7H3 expression of tumor and exist Meningeal Metastases. |
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| Measure | Description | Time Frame |
|---|---|---|
| Clinical response | Evaluate the clinical response of QH104 cell injection in treating B7H3+ solid tumor meningeal metastases according to the Response Assessment in Neuro-Oncology (RANO) criteria | day14 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival(OS) | OS is defined as the time from QH104 cells infusion to the date of death. | 3month,6month,12month |
| Incidence of Adverse Events (AEs) | AE is defined as any adverse medical event from the date of infusion to 14 days after QH104 infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0. |
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Inclusion Criteria:
Age ≥18 years;
Have a histologically or cytologically confirmed solid malignant tumor with positive B7H3 expression;
ECOG ≤ 2 or KPS ≥ 60;
Life expectancy ≥ 8 weeks as assessed by the investigator;
Meningeal metastases (or with brain parenchymal metastases) from any solid malignancy that is refractory to standard treatment or for which no standard treatment is available and positive cerebrospinal fluid (CSF) cytology;
Substantially normal bone marrow reserve function and normal hepatic and renal function (laboratory tests are required to be satisfied prior to first treatment with QH104 Cell Injection):
White blood cell count (WBC) ≥ 3 x 109/L; Lymphocyte count (LY) ≥ 0.8 x 109/L; Hemoglobin (Hb) ≥ 90 g/L; Platelet (PLT) ≥90×109/L; Albumin transaminase (ALT) & albumin transaminase (AST) < 1.5 x ULN; Serum creatinine (Cr) < 1.5 x ULN; Total bilirubin < 1.5 x ULN; PT & PTT ≤ 1.25 × ULN.
Pregnancy test should be negative for women of childbearing potential and both men and women agree to use effective contraception during treatment and for 1 year thereafter;
Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;
Sign the trial informed consent form.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ning Li, Ph.D | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Beijing | Beijing Municipality | 100021 | China |
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| ID | Term |
|---|---|
| D055756 | Meningeal Carcinomatosis |
| ID | Term |
|---|---|
| D008577 | Meningeal Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
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| day14 and day 28 |
| quality of life(QoL) score | Use the M.D. Anderson Symptom Inventory for Brain Tumors (MDASI-BT) to evaluate quality of life for all enrolled subjects, with assessments conducted prior to each cell infusion and during follow-up. | day 14 and day 28 |
| Pharmacokinetic (PK) | Assess the pharmacokinetics (PK) of QH104 cell infusion in B7H3+ solid tumor meningeal metastases by monitoring the quantity of CAR+ cells, their subpopulations following QH104 cell reinfusion. | At days 0, 1, 3, 7, and 14 |
| Pharmacodynamic (PD) | Assess the pharmacodynamics (PD) of QH104 cell infusion in B7H3+ solid tumor meningeal metastases by monitoring the quantity of CAR+ cells, their subpopulations, differentiation, exhaustion, and cytokine changes in the cerebrospinal fluid following QH104 cell reinfusion. | At days 0, 1, 3, 7, and 14 |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |