Bone and soft tissue sarcomas
Conditions
Interventions
Group A:Subjects were infused intravenously with Anti-B7-H3-UCAR-T cells at a dose of 1E6/kgBW.
Group B:Subjects were infused intravenously with Anti-B7-H3-UCAR-T cells at a dose of 5E6/kgBW.
Sponsors
Shanghai Changzheng Hospital
Eligibility
Sex/Gender
All
Age
10 Years to 65 Years
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria to participate in this study: (1) Patients have fully understood this study and voluntarily signed the Informed Consent Form (ICF), and they are willing to comply and cooperate with the follow-up. (2) Age =10 years old, gender is not limited; (3) Patients with histologically confirmed relapsed/refractory bone and soft tissue sarcomas that have failed first-line and/or second-line treatment (disease progression or recurrence or intolerable) or lack of effective therapies; (4) At least one measurable lesion according to RECIST (V1.1) criteria. The puncture biopsy before and after drug administration as judged by the investigator based on patient condition; (5) Eastern Cooperative Oncology Group (ECOG) physical status score: 0-2; (6) Estimated life expectancy is greater than 3 months; (7) Patients are required to undergo lesion detection before enrollment (immunofluorescence testing of fresh tumor tissue samples obtained by puncture biopsy, or immunohistochemistry/immunofluorescence staining of surgically resected tissue wax-ups within the last 1 year), and the expression of B7-H3 in their tumor cells is required to be more 70%; (8) Major organ function needs to meet the following criteria prior to treatment (no transfusion of blood, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), etc., within 14 days prior to the screening period examination): Hematology: ? Absolute neutrophil count >= 1.0 × 10^9 /L. ? Platelets >= 75 × 10^9 /L. ? Hemoglobin >= 80 g/L. Renal function: ? Serum creatinine 30 mL/min, except for acute CrCl decline caused by the disease itself. Liver function: ? Total bilirubin <= 1.5 × ULN (patients with liver metastases, bile duct obstruction, or confirmed Gilbert's syndrome: <= 3 × ULN). ? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 × ULN (patients with liver metastases: <= 5 × ULN). Coagulation function: ? International normalized ratio (INR) or prothrombin time (PT) <= 1.5 × ULN; ? Activated partial thromboplastin time (APTT) <= 1.5 × ULN; (9) Non-surgically sterilized or female subjects of childbearing age, and male subjects whose partner is a female of childbearing age, are required to use contraception [e.g., intrauterine device (IUD), birth control pills, or condoms] during the study treatment period and for 6 months after the end of the treatment period of the study. Female patients of childbearing potential must have a negative blood pregnancy test result within 7 days prior to study entry; and must not be lactating.
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria will be excluded: (1) Patients with a history of severe drug allergies or sensitivities. (2) Patients with the presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrollable or require treatment. (3) Patients with end-stage renal failure. (4) Patients who have mental illness and severe cognitive impairment. (5) Patients who have participated in another clinical trial within 1 month prior to enrollment. (6) Patients who have previously received CAR-T therapy targeting any target. (7) Patients who have received any kind of treatment targeting B7-H3. (8) Patients with another malignancy are excluded, except for those with a locally curable malignancy that has been cured or has persisted in a disease-free state for five years. (9) People with autoimmune diseases (ADs) or non-ADs that cause central nervous system disorders, including epilepsy, psychosis, organic encephalopathy syndromes, cerebrovascular accidents, encephalitis, and central nervous system vasculitis. (10) Patients received antitumor therapy, such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or other investigational drug therapy not listed, within two weeks prior to signing the informed consent form. (11) Patients who have undergone major surgery or have not fully recovered from any previous invasive operation within four weeks prior to receiving the first dose of the study drug. (12) Patients were treated with systemic corticosteroids (prednisone at a dose greater than 10 mg/day, or an equivalent dose of another corticosteroid) or other immunosuppressive therapy within one week prior to signing the Informed Consent Form (ICF), except for topical, ocular, intra-articular, intranasal, or inhaled corticosteroid therapy, or short-term prophylactic corticosteroid use (e.g., to prevent contrast media allergy). (13) Patients had an infection within two weeks prior to enrollment that required systemic (oral or intravenous) anti-infective therapy, except for uncomplicated urinary or respiratory tract infections. (14) Patients has received an inactivated or live-attenuated vaccine, or a novel coronavirus vaccine, within four weeks prior to receiving the first dose of the study drug. (15) Patients with a history of severe cardiovascular disease, such as severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention or second- or third-degree atrioventricular block), myocardial infarction, unstable angina pectoris, or heart failure classified as NYHA class II or higher within the six months prior to the first dose of the study medication. Patients with a left ventricular ejection fraction (LVEF) of less than 55% and a QTcF of greater than 450 milliseconds in men or greater than 470 milliseconds in women during the screening period. (16) Adverse effects of prior antitumor therapy that have not recovered to a CTCAE V5.0 grade rating of <= 1 (except for toxicities such as alopecia, etc., which are judged by the investigator to pose no safety risk). (17) Patients with clinically symptomatic central nervous system metastases or meningeal metastases, or other evidence that the patient's central nervous system metastases or meningeal metastases have not yet been controlled and are judged by the investigator to be unsuitable for enrollment. (18) Those with pleural/abdominal fluid or pericardial effusion wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate, ORR;DCR;disease control rate, DOR;progression-free survival, PFS;Overall survival, OS; | — |
Countries
China
Contacts
Public ContactJianru Xiao
Shanghai Changzheng Hospital
Outcome results
None listed