Anaplastic thyroid cancer
Conditions
Interventions
Experimental group:NKG2D CAR-NK cells with PD-1 monoclonal antibody
Sponsors
Zhejiang Provincial People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Age between 18 and 75 years (inclusive), both males and females are eligible. 2.Histologically confirmed anaplastic thyroid cancer; either not completely resectable by surgery or recurrent after surgery, with BRAF(-) on genetic testing, or BRAF(+) but refusing or unable to use BRAF-related targeted drugs, or progression after treatment with BRAF-related targeted drugs. 3.ECOG performance status score of 0-1, able to tolerate comprehensive treatments including surgery, chemotherapy, radiotherapy, and immunotherapy. Agree to provide tumor tissue samples and peripheral blood for testing and preparation of CAR-NK cells. 4.Able to cooperate in providing tumor tissue samples and peripheral blood for laboratory tests related to the research. 5.Expected survival period of the subject is >=12 weeks. 6.The subject must have at least one target lesion that can be stably evaluated according to RECIST V.1.1 criteria via CT, MRI, or PET-CT. The target lesion must have measurable dimensions (tumor lesion with a long diameter >=10 mm on CT scan, lymph node lesion with a short diameter >=15 mm on CT scan, with a scan thickness not exceeding 5 mm). 7.The subject has adequate organ and bone marrow function. Laboratory screening must meet the following criteria, with all laboratory test results within the specified stable ranges and without ongoing supportive treatment. a) Blood tests: WBC >= 1.5×10^9/L; PLT >=60×10^9/L; Hb >=8.0g/dL; LYM>=0.4×10^9/L; b) Blood biochemistry: Serum creatinine 1.5 × ULN, creatinine clearance rate must be >50mL/min (calculated by Cockcroft-Gault formula); Serum total bilirubin <=1.5×ULN, ALT <=2 ×ULN, AST <= 2 ×ULN (for patients with liver metastasis or liver cancer, ALT <=5×ULN, AST <=5×ULN). c) Amylase and lipase <= 1.5 × ULN; d) Urinalysis: Urine protein < 2+. 8.Fertility status: Female patients of childbearing potential or male patients with female partners of childbearing potential must be willing to use effective contraception from the time of signing the informed consent until 6 months after the last cell infusion (women of childbearing potential include premenopausal women and women within 2 years of menopause). 9.The subject must sign and date a written informed consent form. 10.The subject must voluntarily and be able to comply with the planned treatment, laboratory tests, follow-up, and other study requirements.
Exclusion criteria
Exclusion criteria: 1.Women who are pregnant, or breastfeeding but unable to use artificial feeding. 2.Known history of human immunodeficiency virus (HIV) infection; acute or chronic active hepatitis B (HBsAg positive); acute or chronic active hepatitis C (HCV antibody positive). Syphilis antibody positive; EB virus DNA quantification >200 copies; cytomegalovirus (CMV) infection (IgM positive). 3.Severe infections that are active or clinically poorly controlled. 4.Current presence of heart disease requiring treatment or hypertension judged by the investigator as poorly controlled (defined as systolic blood pressure >=140 mmHg and/or diastolic blood pressure >90 mmHg after standardized antihypertensive treatment). 5.Presence of any of the following cardiac clinical symptoms or diseases: a) Myocardial infarction within the past six months, and the relevant specialist considers the infarction uncontrollable or unpreventable; b) Resting electrocardiogram showing QTc >450ms (male) or QTc >470ms (female) and refusal of preventive regulation or monitoring of cardiac electrical conduction; c) Resting electrocardiogram showing clinically significant abnormalities (e.g., heart rate, conduction, morphological features, etc.) or complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval >250ms, and refusal of preventive interventions such as pacemaker implantation; d) Factors increasing the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in first-degree relatives under 40 years old, or concomitant use of drugs that prolong the interval, and assessed by the relevant specialist as high risk for cardiac arrest or malignant arrhythmia. 6.Abnormal coagulation function (INR >1.5 × ULN), bleeding tendency, or undergoing thrombolytic or routine anticoagulation therapy (e.g., warfarin or heparin), patients requiring long-term antiplatelet therapy (aspirin, dose >300mg/day; clopidogrel, dose >75mg/day), and unable to switch to low molecular weight heparin anticoagulation. 7.Subjects requiring systemic treatment with corticosteroids or other immunosuppressive drugs during the treatment period. 8.Pre-treatment oxygen saturation 15mg/day prednisone within 4 weeks before treatment, excluding inhaled steroids. 10.Patients with current or history of central nervous system diseases, such as seizures, cerebral ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases involving the central nervous system; symptomatic central nervous system metastases or meningeal metastases, or other evidence indicating uncontrolled central nervous system or meningeal metastases, judged by the investigator as unsuitable for enrollment. 11.Current interstitial lung disease, pneumonia, pulmonary fibrosis, acute lung diseases, etc. 12.Previous treatment with NK or CAR-NK immune cell therapy. 13.Treatment with anti-PD-1/PD-L1 monoclonal antibodies within 4 weeks before treatment. 14.Subjects who have previously received other gene therapies. 15.Subjects with severe psychiatric disorders and lacking civil capacity. 16.Participation in other clinical studies within the past month without completing the washout period. 17.Invest
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerance at day 28;Tolerance at day 28;Objective tumor response rate;Duration of remission;Progression free survival;Overall survival;Cytokine; | — |
Secondary
| Measure | Time frame |
|---|---|
| NKG2D CAR-NK cell copy number;NKG2D CAR-NK survival time; | — |
Countries
China
Contacts
Public ContactMinghua Ge
Zhejiang Provincial People’s Hospital
Outcome results
None listed