İlerlemiş Kolorektal Kanserin Tedavisinde PD-1 Geni Devre Dışı Bırakılmış Tümör İçine Sızmış T Hücrelerinin (TIL) Güvenliği ve Tolere Edilebilirliği Üzerine Çalışma

Sade dilde özet

Bu Faz 1 (Phase 1) çalışmada, ilerlemiş kolorektal kanserli (advanced colorectal cancer) hastaların tümör dokusundan alınan tümör içine sızmış T hücreleri (tumor-infiltrating lymphocytes, TIL) laboratuvarda çoğaltılıyor, PD-1 geni devre dışı bırakılacak şekilde düzenleniyor ve kalite kontrolünden sonra hastaya geri veriliyor. Çalışmanın amacı, kilogram başına farklı hücre dozlarının güvenliğini ve tolere edilebilirliğini incelemektir. Çalışmaya, standart tedaviye uygun olmayan, doku alımı için ameliyat veya biyopsiye gönüllü olan 18-70 yaş arası hastalar alınmaktadır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Faz 1 (Phase 1)

Durum

Katılımcı alıyor

Sponsor

Ruijin Hospital

Müdahale

transfusion of 5×10^8 PD-1 knockout TILs per kg body weight, transfusion of 1×10^9 PD-1 edited TILs per kg body weight, transfusion of 2×10^9 PD-1 edited TILs per kg body weight, transfusion of maximum dose without side effects among group A, B and C

Başlangıç

31.12.2024

Tahmini bitiş

01.12.2026

Ülkeler

China

İlgili genler

Merkezler

• Shanghai, China

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

Inclusion Criteria:

* Patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage.
* Patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation.
* Aged ≥18 and ≤70 years old.
* At least one tumor lesion that could be evaluated according to RECIST, version 1.1.
* ECOG score was 0 or 1.
* Adequate bone marrow and organ function.
* The expected survival time of the enrolled patients was no less than 6 months.

Exclusion Criteria:

* Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, traditional Chinese medicine with anti-tumor indications and other anti-tumor treatments within 2 weeks before sampling, except the following:

  1. Nitrosourea or mitomycin C within 6 weeks before surgery;
  2. Oral fluorouracils and small molecule targeted drugs for 1 week before surgery.
* Received other unmarketed investigational drug or treatment within 4 weeks before sampling;
* Had undergone major organ surgery (excluding needle biopsy) within 4 weeks before sampling or had significant lesions Trauma, or the need for elective surgery during the trial;
* Received systemic glucocorticoid (prednisone \>10mg/ day or equivalent dose) or other immunosuppressive therapy within 14 days before sampling; Treatment with topical, ocular, intra-articular, nasal, and inhaled glucocorticoids was excluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrast allergy)
* Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferin, etc., within 14 days before sampling;
* Administration of live attenuated vaccine within 4 weeks before sampling;
* The toxicity of previous antineoplastic therapy has not recovered to CTCAE 5.0 grade ≤1 (except for alopecia and other researchers who judged that there was no safety risk);
* Patients with symptomatic central nervous system or leptomeningeal metastases or other evidence of uncontrolled central nervous system or leptomeningeal metastases as judged by the investigator to be ineligible for enrollment;
* Patients with active infection within 1 week before sampling and currently requiring systemic anti-infective treatment;
* A history of immunodeficiency, including positive HIV antibody test;
* Hepatitis B (HBsAg positive and/or hepatitis C (anti-HCV positive) and/or treponema pallidum antibody positive;
* Patients with current interstitial lung disease;
* Has a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

  1. severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, etc.
  2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose of dose.
  3. New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) \<50%, or structural heart disease at high risk as judged by other investigators;
  4. clinically uncontrolled hypertension.
* Patients with active or previous autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and well-controlled type I diabetes;
* Received immunotherapy with grade ≥ 3 irAE;
* Clinically uncontrollable serous cavity effusion, which was judged by the investigator as not suitable for enrollment;
* Known alcohol or drug dependence;
* Persons with mental disorders or poor compliance;
* Pregnant or lactating women;