Safety and Efficacy Evaluation of MUC-1 CART in the Treatment of Intrahepatic Cholangiocarcinoma
Intrahepatic Cholangiocarcinoma
About this trial
This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma focused on measuring ICC, Mucin-1, CAR-T, Immunotherapy
Eligibility Criteria
Inclusion Criteria:
- Age 18-65 years old.
- The expression of ST glycosylated MUC-1 was more than 1+ in immunohistochemistry(IHC) by applicant-approved laboratory.
- Histopathology or cytology confirmed intrahepatic cholangiocarcinoma.
- Patients who are unable to perform surgery or are not suitable for surgery, or who have recurrence after surgery, or who are unwilling to undergo chemotherapy.
- With at least one extracranial measurable lesion according to RECIST 1.1 edition.
- The expected survival time is more than 60 days.
- The main organs are functional and meet the following criteria:
1) ECOG physical fitness score was 0~1 or KPS score >70. 2) Routine blood tests were in accordance with the following criteria: HB (>90 g/L) (no blood transfusion within 14 days), ANC (>1.5 x10^9/L), PLT (> 80 x10^9/L), lymphocyte (> 0.7 x10^9/L), LY (> 15%), Alb (> 2.8 g/dL), serum lipase and amylase < 1.5^ULN (upper limit of normal value).
3) Biochemical examination should meet the following criteria: TBIL < 1.5x ULN (upper limit of normal value); ALT < 2.5 xULN; serum Cr<1 xULN; endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula).
4) Cardiac ejection fraction >55%. 8. No active hemorrhagic disease or severe coagulation dysfunction. 9. No allergy to the contrast media. 10. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the results are negative, and are willing to use appropriate contraception methods during the experiment and 8 weeks after the last CART.
11. The volunteers voluntarily joined the study, signed informed consent, and had good compliance and follow-up.
Exclusion Criteria:
- The transduction efficiency of T cells was <10% or T cells expanded less than 5 times after culture.
- Chimeric antigen receptor therapy or other transgenic T cell therapy.
- Pregnant or lactating women.
- In the first 4 weeks before the start of the study, they took part in other drug clinical trials.
- Patients with hypertension who can not be well controlled by a single antihypertensive drug (SBP> 140 mmHg, DBP> 90 mmHg), myocarditis or congenital heart disease, myocardial ischemia or infarction above grade I, arrhythmia above grade I (including QT interval < 440 ms) or cardiac insufficiency.
- Long term unhealed wounds or fractures.
- With a history of psychotropic substance abuse and unable to quit or have a history of mental disorders.
- Past and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc.
- With uncontrollable fungi, bacteria, viruses or other infections, or need antibacterial treatment. The presence of simple urinary tract infections and uncomplicated bacterial pharyngitis is allowed after consultation with a medical supervisor, if there is a response to active therapy.
- According to the NCI-CTCAE 4.0 standard, the patients who had used chemotherapy in the past had grade 2 hematological toxicity or grade 3 non-hematological toxicity.
- With a history of HIV or hepatitis B or hepatitis C virus infection.
- There are any indwelling catheters or drainage tubes (e.g. percutaneous nephrostomy, Frey's catheter, bile drainage or pleural/peritoneal/pericardial catheter). The use of dedicated central venous catheters is permitted.
- With brain metastases.
- With a history or disease of CNS, such as epileptic seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS.
- With a major immunodeficiency.
- The main therapeutic drugs in this study (including fludarabine, cyclophosphamide, sodium mesylate, tropizumab and anti-infective drugs used during pretreatment) had a history of severe hypersensitivity.
- In the first 6 months of admission, there was a history of deep venous thrombosis or pulmonary embolism.
- History of autoimmune diseases (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that cause terminal organ injury or require systemic immunosuppressive/systemic disease-regulating drugs.
- With any diseases that may interfere with the safety or efficacy of treatment.
Sites / Locations
- The second affiliated hospital of Zhejiang UniversityRecruiting
Arms of the Study
Arm 1
Experimental
MUC-1 CART
Patients are given fludarabine and cyclophosphamide as pretreatment before MUC-1 CART immunotherapy. After treatment, specific antibodies, CART cells and serum levels of cytokines will be assessed.