A Clinical Study to Evaluate the Safety and Efficacy of Autologous Tumor Infiltrating Lymphocytes Injection in Patients With Advanced Hepatobiliary-Pancreatic Cancers

Trial ID: NCT05098197

Interventional - Phase 1 - Recruiting

This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with advanced hepatobiliary-pancreatic cancers. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.

Conditions

• Advanced Liver Cancers
• Tumor Infiltrating Lymphocyte
• Treatment Side Effects
• Effects of Immunotherapy
• Advanced Pancreatic Cancers

Interventions

• Tumor Infiltrating Lymphocyte

Eligibility

Inclusion criteria

• 1. Age: 18 years to 75 years;
• 2. Histologically diagnosed as primary/relapsed/metastasized hepatobiliary cancer or pancreatic cancers;
• 3. Expected life-span more than 3 months;
• 4. Karnofsky≥60% or ECOG score 0-2;
• 5. Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
• 6. Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
• 7. At least 1 evaluable tumor lesion;
• 8. Hematology and Chemistry（within 7 days prior to enrollment）:
• Absolute count of white blood cells≥2.5×10\^9/L;
• Absolute count of neutropils≥1.5×10\^9/L;
• Absolute count of lymphocytes ≥0.7×109/L；
• Platelet count≥100×10\^9；
• hemoglobin≥90 g/L;
• Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
• International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
• Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min;
• Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN);
• Totol bilirubin≤1.5×ULN;
• 9. no absolute or relative contraindications to operation or biopsy;
• 10. Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion；
• 11. Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;
• 12. Be able to understand and sign the informed consent document;
• 13. Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion criteria

• 1. Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
• 2. Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
• 3. Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
• 4. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
• 5. Severe physical or mental diseases;
• 6. Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
• 7. Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
• 8. History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
• 9. Having received immunotherapy and developed irAE level greater than Level 3;
• 10. Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
• 11. Females in pregnancy or lactation;
• 12. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
• 13. Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Sponsor

Shanghai Juncell Therapeutics, Shanghai 10th People's Hospital

Source: ClinicalTrials.gov

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