Biliary Tract Cancer
Conditions
Interventions
Dose-escalation group:Super circulating tumor infiltrating lymphocytes
Dose-expansion group:Super circulating tumor infiltrating lymphocytes
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: (1) Aged 18 to 70 years old, regardless of gender. (2) Expected survival time is greater than three months. (3) Patients with locally advanced or metastatic biliary tumors confirmed by histology or cytology have failed previous treatment or have given up radiotherapy and chemotherapy and will voluntarily accept the cell therapy. (4) At least one measurable target lesion by CT or MRI as defined by RECIST v1.1. The measurable tumor lesion is defined as the longest diameter >= 10mm and the scan thickness does not exceed 5.0mm. For lymph node lesions, the short diameter is >= 15mm. (5) Willing to draw peripheral blood through the vein, and there is no contraindication for the collection of peripheral blood mononuclear cells. (6) The proportion of peripheral blood PD1-positive T cells in total T cells is >= 18% for the patients who have not been treated with PD-1 monoclonal antibody. The proportion of peripheral blood PD1-positive T cells in total T cells is >= 12% and the proportion of Treg in PD1-positive T cells does not exceed 20% for the patients who have been treated with PD-1 monoclonal antibody. (7) Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. (8) No serious hematology, liver, and kidney dysfunction, meet the following laboratory test results: i. Hematology: neutrophils >= 1.5 * 10^9 / L, platelets >= 75 * 10^9 / L, hemoglobin >= 90g / L; total lymphocytes >= 50% of the normal lower line; ii. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 60mL / min using the Cockcroft-Gault formula; iv. Coagulation function: prothrombin time (PT) = 3.0g/dl. (9) Toxicity caused by previous treatment, surgery or radiation must have been alleviated to baseline or <= Grade 1, assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE 5.0). (Except for alopecia or vitiligo; Neuropathy induced by previous antitumor treatment is stable or <= Grade 2). (10) Male or fertile female subjects took effective contraceptive measures during the treatment period and within 90 days after the last medication; (11) Ability to follow clinical research protocols and follow-up procedures. (12) Patients must have the ability to understand the study protocol and are willing to participate in the study and provide written informed consent.
Exclusion criteria
Exclusion criteria: (1) Central nervous system (CNS) metastases from central nervous system disease or clinically unstable tumors. Clinically stable tumor CNS metastasis means that the disease is stable for >= 3 months confirmed by the MRI or CT, and / or that the condition is controllable through low doses of steroid hormones, antiepileptics and other relief drugs. (2) Accept any organ transplant, including allogeneic stem cell transplants, except those transplants that do not require immunosuppression (eg,corneal transplants, hair transplants). (3) Presence of major acute or chronic infections, including: i. Poorly controlled hepatobiliary infections, including cholangitis, intrahepatic biloma, abscesses, etc. or complications after untreated examination or post-stent placement. ii. A known history of positive human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome (not required for screening). If the investigator strongly suspects HIV infection in a subject with no known medical history during the screening period, the subject should be tested for HIV according to local standard guidelines). iii. Active TB infection (clinical symptoms, physical examination or imaging, and laboratory findings. iv. An active bacterial or fungal infection that requires systemic treatment. v. Viral hepatitis, including hepatitis B and C, etc. vi. Patients with syphilis virus positive (4) Patients have autoimmune diseases. (5) A history or current history of steady state change of calcium and phosphorus such as parathyroid disorder, tumor lysis syndrome etc. (6) Acute exacerbation of chronic obstructive pulmonary disease , or other respiratory disease that was hospitalized within 30 days before enrollment or hinders study treatment. (7) Prior treatment-related toxicity that is greater than Grade 1 by the NCI CTCAE 5.0 persists (except for hair loss and vitiligo), but sensory neuropathy that is less than Grade 2 is acceptable. (8) Clinically significant cardiovascular or cerebrovascular diseases, such as: cerebrovascular accident or stroke (less than 6 months before the enrollment), myocardial infarction (less than 6 months before the enrollment), unstable angina, congestive heart failure ( Greater than or equal to New York Heart Association Grade II) or severe arrhythmia, including QTc interval is greater than 480ms. (9) The patients who received chemotherapy and hormone (adrenocortical hormone) treatment within 2 months before the start of screening. (10) Received colony stimulating factor, erythropoietin, blood transfusions within 2 weeks before the start of the screening. (11) Live vaccines were given within 1 year before the start of the screening. Allow inactivated vaccines (eg inactivated influenza vaccine); (12) The subjects can not tolerate or are allergic to contrast agents of CT or magnetic resonance imaging (MRI) according to the investigators judgment. (13) Pregnant or lactating women. (14) Have a history of alcohol or drug abuse within 2 years (Learned through inquiries and previous medical history) (15) Other severe acute or chronic diseases, or incapacity or limited capacity for civil conduct. (16) Patients or family members could not understand the conditions and goals of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR;DOR;PFS;OS;vital signs;Physical examination;Adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Detection of ScTIL-v2 in peripheral blood;Detection of Lentivirus Copy Number; | — |
Countries
China
Contacts
Public ContactHaitao Zhao
Peking Union Medical College Hospital
Outcome results
None listed