| 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:
1. ECOG physical condition score is 0~1 or KPS score is >70;
2. 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).
3. 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);
4. 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;
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.
|
