CART Therapy in Digestive System Tumors

This is an interventional treatment trial for Malignant Neoplasms of Digestive Organs Read More

Inclusion Criteria:

1. Aged between 18 and 70;
2. Positive expression of immunohistochemical (IHC) assay targets in a laboratory approved by the partner;
3. Pathology confirmed digestive tract tumor;
4. Patients who have failed or relapsed after at least the first and second line standard treatment, and patients who are intolerant to or voluntarily give up the standardized treatment;
5. At least one extracranial measurable lesion according to RECIST1.1 or EORTC or PERCIST;
6. Expected survival ≥90 days;

7. The main organs are functioning normally, i.e. they meet the following criteria:

   • ECOG physical condition score is 0~1 or KPS score is >70;
   • serum test criteria were as follows: HB≥90g/L (no blood transfusion within 14 days), ANC≥ 1.5 x 10^9/L, PLT≥80 x 10^9/L, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×ULN (upper limit of normal value).
   • Biochemical examination shall meet the following standards: TBIL≤ 1.5x ULN (upper limit of normal value); ALT and AST≤ 2.5x ULN; ALT and AST≤5xULN in case of liver metastasis; Serum Cr≤1xULN, endogenous creatinine clearance rate >50 ml/min (Cockcroft-Gault formula);
   • cardiac ejection fraction >55%;
8. No hemorrhagic disease or coagulation disorder;
9. No allergy to the developer;
10. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days prior to enrollment, with negative results, and be willing to use an appropriate method of contraception during and 8 weeks after the last dose of CART (women who have undergone sterilization or have been postmenopausal for at least 2 years may be considered sterile);
11. The subjects voluntarily joined the study, signed the informed consent form, had good compliance and cooperated with the follow-up.

Exclusion Criteria:

1. T cell transduction efficiency <5% or T cell amplification < 2 times after culture;
2. Participated in other drug clinical trials within 4 weeks before the start of the study;
3. Patients with hypertension and unable to obtain good control by single antihypertensive drugs (systolic blood pressure > 140 mmHg, diastolic blood pressure b> 90 mmHg, the specific conditions shall be evaluated by the researchers) have myocardial ischemia or infarction of grade I or above, arrhythmia of grade I or above (including QT interval ≥ 440ms) or cardiac insufficiency;
4. A wound or fracture in the chest or other area that has not healed for a long time;
5. Has a history of substance abuse and is unable to quit or has a history of mental disorders;
6. Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severe pulmonary function impairment, etc.;
7. Fungus, bacteria, virus or other infection that cannot be controlled or requires antibiotic treatment. The presence of a simple urinary tract infection and uncomplicated bacterial pharyngitis is permitted after consultation with a medical supervisor;
8. For subjects who have used chemotherapy before, according to NCI-CTCAE 4.0, there is grade ≥2 hematological toxicity or grade ≥3 non-hematological toxicity at the time of enrollment;
9. A known history of HIV, or a positive nucleic acid test for hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive);
10. The presence of any indwered catheter or drainage tube (e.g., bile drainage tube or pleural/peritoneal/pericardial catheter). The use of specialized central venous catheters was permitted (the influence of fistula, percutaneous nephrostomy, and indwsed Foley catheters in colorectal cancer patients was considered by the investigators);
11. Brain metastases; A history or medical condition of CNS, such as seizure disorder, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS;
12. metastases to brain;
13. Significant immunodeficiency;
14. The major therapeutic drugs in this study (including fludalabine, cyclophosphamide, sodium meth, and tozumab and anti-infective drugs used to prevent and treat CRS) have a history of severe hypersensitivity reaction;
15. History of deep vein thrombosis or pulmonary embolism 6 months before enrollment;
16. A history of an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has resulted in injury to the terminal organs or that requires systemic immunosuppressive/disease-modulating drugs in the past 2 years;
17. Any disease that may interfere with the evaluation of the safety or efficacy of the study treatment.