| Eligibility |
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.
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