Advanced solid tumor
Conditions
Interventions
experimental group:autologous CAR-T cell therapy
Sponsors
Shanghai Changhai Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. The age is between 18-70 years (including the boundary value), both male and female; 2. Subjects with advanced malignant solid tumors with positive expression of CLDN18.2 confirmed by histology or cytology (including advanced gastric cancer or esophagogastric junction adenocarcinoma, advanced pancreatic cancer, and metastatic ovarian cancer without standard treatment options) ; 3. All subjects are required to provide tumor tissue samples that can be used for CLDN18.2 analysis, which need to be tumor histopathological samples within 24 months before signing the informed consent form, or fresh biopsies collected within 6 months before cell reinfusion Specimens; biopsy tumor tissue specimens are positive for CLDN18.2 histological staining (defined as staining intensity >= 1+, positive rate >= 10%), the recommended antibody for detection is: Anti-Claudin18.2 antibody; 4. The expected survival period of the subject is >= 12 weeks; 5. According to the RECISTV.1.1 standard, subjects participating in dose escalation must have at least one target lesion that can be evaluated stably; 6. ECOG physical status score 0-1; 7. Subject has adequate organ and bone marrow function. Laboratory screening must meet the following criteria (refer to NCICTCAE5.0). All laboratory tests should have results within the following stable range without ongoing supportive treatment: (1) Blood test: white blood cell >= 1.5 x 10^9/L; platelet count >= 100 x 10^9/L; hemoglobin >= 9.0 g/dL; lymphocyte >= 0.4 x 10^9/L; (2) Liver function: serum total bilirubin 1.5 x ULN, creatinine clearance > 50 mL/min (according to the Cockcroft-Gault formula: ((140-age) x body weight (kg) x 0.85, only For women))/72 x creatinine (mL/dL)); urine protein qualitative = 2+, 24h urine protein quantitative test is required (if 24h urine protein quantitative test < 1 g, it is acceptable ); (4) Amylase and lipase <= 1.5 x ULN; (5) Coagulation function: international normalized ratio (INR) <= 1.5 x ULN, activated partial thromboplastin time (APTT) <= 1.5 x ULN; 8. All toxic reactions caused by previous anti-tumor therapy have been relieved to grade 0-1 (according to NCICTCAE version 5.0) or to an acceptable level for the inclusion/exclusion criteria. Except for hair loss, vitiligo and other toxicities that the researchers believe do not pose a safety risk to the subjects; 9. Fertility status: Female patients of childbearing age or male patients whose sexual partner is a woman of childbearing age are willing to take medically approved high-efficiency contraceptive measures such as intrauterine contraceptives from signing the informed consent to 6 months after the last cell infusion or condoms (women of reproductive age include premenopausal women and women within 24 months of postmenopause); 10. The subject must sign a written informed consent form and indicate the date; 11. The subjects must be voluntary and able to comply with the predetermined treatment plan, laboratory tests, follow-up and other research requirements.
Exclusion criteria
Exclusion criteria: 1. Pregnant and lactating women; 2. Known history of human immunodeficiency virus (HIV) infection; acute or chronic active hepatitis B (positive for HBsAg or HBsAb, and positive for HBV-DNA); acute or chronic active hepatitis C (positive for HCV antibody , and HCV-RNA was positive). Syphilis antibody positive; Epstein-Barr virus DNA quantification > 500 copies (or according to the positive detection standard of each research center); cytomegalovirus (CMV) infection (IgM positive); 3. Severe infection in active stage or poor clinical control; 4. There is currently a heart disease that needs treatment or hypertension that is poorly controlled by the investigator (defined as systolic blood pressure >= 140 mmHg and/or diastolic blood pressure > 90 mmHg after standardized antihypertensive drug treatment); 5. Any of the following cardiac clinical symptoms or diseases existed within 6 months before cell reinfusion: (1) New York Heart Association (NYHA) >= grade II cardiac insufficiency; or left ventricular ejection fraction (LVEF) 450 ms (male) or QTc > 470 ms (female); (4) Abnormalities with important clinical significance (such as abnormalities in heart rate, conduction, and morphological characteristics) or complete left bundle branch block or third-degree heart block or second-degree heart block or PR interval > 250 ms; (5) There are factors that increase the risk of QTc prolongation and abnormal heart rate, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or sudden unexplained death of immediate relatives under the age of 40, or prolonged Interval concomitant medication; 6. Evidence of major coagulation disorders or other significant bleeding risks, including: (1) Previous history of intracranial hemorrhage or spinal cord hemorrhage; (2) Tumor lesions invading large blood vessels with obvious risk of bleeding; (3) Thrombosis or embolism occurred within 6 months before cell reinfusion; (4) Clinically significant hemoptysis or tumor hemorrhage occurred within 1 month before cell reinfusion; (5) Major trauma or major surgery occurred within 1 month before enrollment; (6) There are any bleeding diseases, such as hemophilia, von Willebrand disease, etc.; (7) Anticoagulant therapy for therapeutic purposes (except low molecular weight heparin) has been used within 2 weeks before cell reinfusion; (8) The patient is receiving conventional anticoagulant therapy (such as warfarin or heparin). Patients need long-term antiplatelet therapy (aspirin, dose > 300 mg/day; clopidogrel, dose > 75 mg/day); dipyridamole, ticlopidine or cilostazol, etc.; 7. Subjects who need to use corticosteroids or other immunosuppressive drugs for systemic treatment during the treatment period. Presence of any active autoimmune disease, or history of autoimmune disease with expected recurrence (including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, need for bronchodilators Asthma subjects undergoing medical intervention. Except for the following conditions: type 1 diabetes; skin diseases (such as vitiligo, psoriasis, alopecia) that do not require systemic treatment; Asthma in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective remission rate;progression free survival;Dose-limiting toxicity;maximum tolerated dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| The number of copies and survival time of cells in vivo;pharmacokinetic evaluation index;exploratory biomarker evaluation index;overall survival; | — |
Countries
China
Contacts
Public ContactLu Zhengmao
Shanghai Changhai Hospital
Outcome results
None listed