Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma

Обзор

This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.

Подробное описание

We designed a clinical study and divided the trial into two phases.

Phase 1 (climbing test) : 12 patients were randomly divided into 4 groups (n=3). 12 patients were treated with cyclophosphamide at the dose of 60mg/kg/d 8-7 days before CAR-T cell infusion, and fludalabine at the dose of 25mg/m\^2/d 6-2 days before CAR-T cell infusion. 5 mg anti-human CAIX monoclonal antibody (G250) was injected into the hepatic artery of each patient by an interventional catheter on the day before CAR-T cells infusion. On Day 0, CAR T cells were injected into patients in group 1, 2, 3 or 4 at the dose of 1x10\^7/ person, 1\*10\^8/ person, 1\*10\^9/ person or 1\*10\^10/ person, respectively. The infusion time is about 15-30min. On day 0-14, IL-2 (75000IU/kg) was injected subcutaneously once a day. From day 15-28, IL-2 (75000IU/kg) was subcutaneously injected into the patients three times a week. The purpose of this study is to assess subjects' MTD (maximum tolerated dose) against CAR T cells.

Phase 2: After determining the appropriate therapeutic dose for patients with renal cell carcinoma, 8 patients received the same pre-treatment of chemotherapy and G250 antibody. Then, the appropriate therapeutic dose of CAR T cells according to the results of phase 1 was infused on Day 0. On day 0-14,IL-2 (75000IU/kg) was given subcutaneously once a day. On day 15-28, IL-2 (75000IU/kg) was given subcutaneously three times a week.

Peripheral blood was collected every 4 weeks to evaluate proliferation and survival of CAR-T cells. After 6 months of close follow-up, subjects will undergo a medical history evaluation, physical examination, and blood tests quarterly for 2 years. After this assessment, subjects will be enrolled in an annual telephone follow-up and questionnaire study for up to five years to evaluate treatment for long-term health problems, such as recurrence of malignant tumors.

Вмешательства

• Биопрепарат CAR-T cell immunotherapy
  This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at CAIX antigen.

Первичные конечные точки

• Safety evaluation:Incidence and severity of adverse events [Срок оценки: First 1 month after CAR-T cells infusion]
• Effectiveness evaluation [Срок оценки: 3 months after CAR-T cells infusion]

Вторичные конечные точки (2)

• Progression-free survival (PFS) [Срок оценки: 24 months after CAR-T cells infusion]
• Overall survival (OS) [Срок оценки: 24 months after CAR-T cells infusion]

Критерии участия

Критерии включения

• Male or female patients aged from 18 to 70 years old;
• The patient's ECOG score is ≤ 2;
• Patients with advanced or metastatic renal cell carcinoma:

(1) have received first-line and second-line targeted therapy in the past; (2) Previous immunization with PD-1/L1 and ≤2 regimens; (3) Unable to tolerate targeted therapy or immunotherapy. 4.There are measurable or evaluable lesions; 5.The main tissues and organs of patients function well:

• liver function: ALT/AST< 3 times the upper limit of normal value (ULN);
• Renal function: creatinine < 220 μmol/L;
• Lung function: indoor oxygen saturation ≥ 95%;
• Cardiac function: Left ventricular ejection fraction (LVEF)≥40% 6.Patients or their legal guardians voluntarily participate and sign informed consent.

Критерии исключения

• Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
• Feasibility assessment and screening showed that the transfection of targeted lymphocytes was less than 10% or the amplification was insufficient (< 5 times) under the co-stimulation of CD3/CD28.
• The vital signs are abnormal, and those who cannot cooperate with the examination;
• Those who have mental or psychological diseases can not cooperate with treatment and efficacy evaluation;
• Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
• Subjects with systemic infection or severe local infection who need anti-infection treatment;
• Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
• Patients with other tumors;
• Doctors believe that there are other reasons that can not be included in the treatment.

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

• Affiliated Hospital of Xuzhou Medical University — Xuzhou

Публикации

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Идентификаторы

NCT: NCT04969354 · XYFY2021-KL092-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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