Colorectal cancer
Conditions
Interventions
Group 2:combined immunotherapy
Sponsors
Peking University Shougang Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: Each patient must meet all of the following criteria before enrolling in the trial: 1. The subject or legal guardian understands the purpose and test procedure of the test, voluntarily participates in the test, and signs an informed consent form; 2. Aged 18 to 80 years old male and female; 3. Diagnosis of stage III or IV stage III or IV colorectal cancer by pathology, histology, cytology or imaging (UICC/AJCC TNM staging system (8th edition, 2017)) is no longer suitable Routine treatment (such as surgery, radiotherapy, chemotherapy, etc.), unresolved after conventional treatment, recurrence after routine treatment, lack of effective treatment or rejection of conventional treatment, and patients who may benefit after including the trial; 4. At least one measurable target lesion at baseline (according to RECIST 1.1); measurable target lesions can meet the following requirements: (1) There is at least one radial line (recorded as the largest diameter) that can be accurately measured. The minimum length is as follows: The minimum length of CT scan is 10mm (CT scan layer thickness is not more than 5mm); if the CT scan layer thickness is >5mm, the minimum lesion size can be measured as twice the layer thickness; The minimum length of the clinical routine examination instrument is 10mm (the tumor lesion cannot be accurately measured by the caliper instrument and should be recorded as unmeasurable); Malignant lymph nodes: pathological enlargement and measurable, CT scan of a single lymph node must be >=15mm (CT scan layer thickness is recommended =3 months; (7) Laboratory test results: Blood routine: white blood cell count (WBC) >=3.0x10^9/L, absolute neutrophil >=1.5x10^9/L; platelet count >=100x10^9/L; hemoglobin >=90g/L; serum albumin = 3.0g /dL; Liver function: serum total bilirubin (TBIL) =50mL/min (Cockroft-Gault formula), and urine protein < 2+ (baseline urine protein 2+, 24-hour urine protein quantitation should be performed, <=1g can only be selected); Coagulation function: International normalized ratio (INR), partial thromboplastin (APTT), partial prothrombin time (PT) <=1.5 ULN within 7 days before the study; Thyroid stimulating hormone (TSH) <= ULN; if TSH is abnormal, T3 and T4 levels should be considered or checked, and those with normal T3 and T4 levels can be selected; (8) Female subjects of childbearing age must undergo a pregnancy test (serum or urine) within 7 days prior to enrollm
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria may not be included in the trial: (1) The patient's T cell or DC vaccine cannot be amplified or prepared in a pre-amplification experiment; (2) Previously received radiotherapy, chemotherapy, surgery, after the completion of treatment (last dose), less than 4 weeks from the first CAR-T cell infusion, oral small molecule chemotherapy or targeted drugs less than 5 half-life; or accepted Nitrosourea and mitomycin C for less than 6 weeks; or adverse events (except for hair loss) caused by prior treatment did not return to CTC AE1 degrees; (3) Patients who have received previous CAR-T cell therapy; (4) Patients with a history of severe drug allergy, or patients known to be allergic to fludarabine (decitabine); (5) There are clinically significant bleeding symptoms or clear bleeding tendency within 3 months before the first CAR-T cell infusion, such as: a history of hemoptysis, coughing blood volume greater than 100ml/24 hours; gastrointestinal bleeding, Hemorrhagic gastric ulcer, fecal occult blood 2+ and above; (6) Imaging shows signs of tumor invasion into large blood vessels. Subjects whose tumors are completely in close, outraged, or invaded into the lumen of the large blood vessels (eg, the pulmonary artery or superior vena cava) must be excluded; (7) CT or MRI scans show signs of brain metastasis or spinal cord compression; or patients have symptoms associated with brain metastases or spinal cord compression; (8) The patient has severe unhealed wounds, ulcers, fractures, or major surgery; or is expected to undergo major surgery during the study; (9) Current or near-term (within the first 10 days of receiving the first CAR-T cell) using a full dose oral or parenteral anticoagulant or thrombolytic agent. However, temporary preventive use of anticoagulant drugs is permitted; (10) The patient has a history of autoimmune diseases (such as hyperthyroidism, inflammatory bowel disease, multiple sclerosis, autoimmune hepatitis, pemphigus vulgaris, pemphigoid, multiple cerebrospinal sclerosing, pulmonary hemorrhagic nephritis) Organ-specific autoimmune diseases such as syndromes and chronic lymphatic thyroiditis; or systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, nodular polyarteritis or Wegener granulomatosis Or any active autoimmune disease at the time of screening, and currently using immunosuppressive drugs (including but not limited to corticosteroids, cyclophosphamide, azathioprine, or not, within the first 14 days of receiving the first CAR-T cell) Methotrexate, thalidomide and anti-tumor necrosis factor (TNF-a) drugs for systemic treatment, but local temporary use of hormones, alternative treatment (such as thyroid hormone, insulin or for adrenal or pituitary insufficiency) Physiological corticosteroid replacement therapy, etc.), can not be ruled out. Glucocorticoid treatment for 48 hours of treatment for allergic reactions to contrast agents, may not be ruled out after approval by the main investigator; (11) Those who have received anti-tuberculosis treatment or have active tuberculosis (TB) within one year before receiving anti-tuberculosis treatment or screening, or have suspicious symptoms, signs or imaging findings of tuberculosis, and judged by relevant researchers and obtained relevant experiments. Patients with positive laboratory tests (such as photomicroscopy, mycobacterial culture, tuberculosis bacillus nucle
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tumor imaging;Cytokine IL-6;Cytokine TNF-a;CRP;Copy numbers of CART in vivo; | — |
Countries
China
Contacts
Public ContactJin Gu
Peking University Shougang Hospital
Outcome results
None listed