A Study of GC201 TIL in Advanced Gynecologic Tumors (10hospital)

Официальное название

A Clinical Study on Signal Switch Receptor Modified Tumor Infiltrating Lymphocytes Injection (GC201 TIL) in Patients With Gynecologic Tumors

Обзор

This study is to investigate the safety and efficacy of signal switch receptor modified TIL (GC201 TIL) in patients with advanced gynecologic tumors. Autologous TILs from tumor resections or biopsies are first gene modified(TGF-β receptor or PD-1 gene modified TILs which could transfer the suppression signal surrounding the microenvironment of tumor bed into persistent T cell activation signal) and than expanded before i.v. infusion into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.

Вмешательства

• Биопрепарат Signal Switch Receptor Modified TIL
  Adoptive transfer of 2x10\^8-1x10\^10 autologous signal switch receptor modified TILs to patients i.v. in 30-120 minutes.

Первичные конечные точки

• Adverse Events (AE) [Срок оценки: Up to 6 months]
• Objective Response Rate (ORR) [Срок оценки: Up to 36 months]
• Disease Control Rate (DCR） [Срок оценки: Up to 36 months]
• Duration of Response (DOR) [Срок оценки: Up to 36 months ]]
• Progression-Free Survival (PFS) [Срок оценки: Up to 36 months]
• Overall Survival (OS) [Срок оценки: Up to 36 months ]]

Вторичные конечные точки (1)

• Change in Quality of Life [Срок оценки: Up to 36 months]

Критерии участия

Критерии включения

• Age: 18 years to 75 years;
• Histologically diagnosed as primary/relapsed/metastasized Gynecological 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: NCT05098171 · GC201-2021-10hospital-Gyne

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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