A Study of GC101 TIL in r/r Gastrointestinal Tumors (10hospital)

Официальное название

A Clinical Safety and Efficacy Study of Autologous Tumor Infiltrating Lymphocytes Injection (GC101 TIL) in Patients With r/r Gastrointestinal Tumors

Обзор

This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with malignant refractory/relapsed gastrointestinal tumors. 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.

Вмешательства

• Биопрепарат Tumor Infiltrating Lymphocytes (TIL)
  Adoptive transfer of 1x10\^9-5x10\^10 autologous TILs to patients i.v. in 30-120 minutes.

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: Up to 36 months]
• Progression-Free Survival (PFS) [Срок оценки: Up to 36 months]

Вторичные конечные точки (3)

• Change in Quality of Life [Срок оценки: Up to 36 months]
• Duration of Response (DOR) [Срок оценки: Up to 36 months]
• Overall Survival (OS) [Срок оценки: Up to 36 months]

Критерии участия

Критерии включения

• Age: 18 years to 75 years;
• Histologically diagnosed as primary/relapsed/metastasized gastrointestinal tumors ;
• Expected life-span more than 3 months;
• Karnofsky≥60% or ECOG score 0-2;
• Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
• Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
• At least 1 evaluable tumor lesion;
• 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;
• no absolute or relative contraindications to operation or biopsy;
• 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；
• Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;
• Be able to understand and sign the informed consent document;
• Be able to stick to follow-up visit plan and other requirements in the agreement.

Критерии исключения

• Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
• Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
• 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.
• 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;
• Severe physical or mental diseases;
• Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
• Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
• History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
• Having received immunotherapy and developed irAE level greater than Level 3;
• 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);
• Females in pregnancy or lactation;
• History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
• Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Tenth People's Hospital — Шанхай

Идентификаторы

NCT: NCT04960072 · GC101-2021-10hospital-GI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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