This clinical trial is designed to study an investigational cell therapy called cCTL-GL01 in patients with advanced gastrointestinal cancers (including cancers of the stomach, esophagus, colon, or rectum) that have not responded well to standard treatments. The main goals of this study are to find out: If cCTL-GL01 is safe and what side effects it might cause; How well cCTL-GL01 works to control or shrink tumors.
cCTL-GL01 is a cellular immunotherapy utilizing specialized T-cells engineered to recognize, target, and eliminate cancer cells. For patients enrolled in this clinical study, the therapeutic process comprises the following phases: Preconditioning (Pre-treatment): Patients undergo a short course of lymphodepleting conditioning to optimize the host immune environment and facilitate the engraftment and expansion of the infused T-cells. cCTL-GL01 Infusion and Combination Therapy: cCTL-GL01 cells are administered via intravenous (IV) infusion, supplemented by a combination therapy designed to enhance the in vivo persistence and therapeutic efficacy of the infused T-cells. Safety and Efficacy Monitoring: Subjects undergo rigorous monitoring to ensure clinical safety and evaluate therapeutic response. This includes active surveillance for immunotherapy-related adverse events (particularly Cytokine Release Syndrome, or CRS), routine laboratory examinations (blood panels), and regular radiographic assessments (e.g., CT or MRI scans) to evaluate tumor response.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Following lymphodepleting conditioning and a 2-3 day chemotherapy washout period, patients will begin receiving twice-weekly infusions of autologous cCTL cells. This study is designed such that the first three cCTL infusions for each patient will follow a stepwise dose escalation of the effective dose, specifically 1-2×107 cCTL/Kg、3-4×107 cCTL/Kg、4-5×107 cCTL/Kg; safety will be evaluated during this period to determine subsequent infusion doses. The target dose for this study is 4-5x107 cCTL/Kg per infusion, with a target frequency of twice weekly. This phase will last 2-3 weeks, with a total of 4-6 infusions. Based on the results of the first course of treatment, the investigator will determine whether to proceed with a second course of treatment. During treatment intervals, the investigator may administer bridging therapy based on the patient's clinical condition.
dose-limiting toxicities (DLTs)
To evaluate safety, the investigator will monitor the number of participants experiencing treatment-related adverse events (AEs) and dose-limiting toxicities (DLTs), assessing their incidence, type, severity, and causality. All AEs, including immunotherapy-related reactions such as cytokine release syndrome (CRS), will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The primary parameters to be evaluated are as follows: ①Blood pressure: Changes in patients' blood pressure will be closely monitored throughout the treatment. The measurement data will be reported and aggregated in millimeters of mercury (mmHg). ②Pulse: Patients' pulse will be continuously monitored throughout the trial to evaluate physiological stability and acute reactions following treatment administration. The measurement data will be reported in beats per minute (bpm). ③Inflammatory Markers: Blood inflammatory markers, specifically C-reactive prote
Time frame: From Week 1 through Week 16 of treatment
Objective response rate (ORR)
The percentage of participants achieving a Complete Response (CR) or Partial Response (PR). Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Up to Week 16 post-treatment (with imaging assessments up to approximately 12 months or until disease progression)
disease control rate (DCR)
The percentage of participants achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD). This will be assessed according to RECIST v1.1.
Time frame: Up to Week 16 post-treatment (with imaging assessments up to approximately 12 months or until disease progression)
Progression-free survival (PFS)
The time from the start of treatment to the date of first documented disease progression (assessed via RECIST v1.1) or death from any cause, whichever occurs first. Measurement data will be reported in weeks or months.
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Time frame: Up to approximately 24 months.
overall survival (OS)
The time from the start of treatment to the date of death from any cause. Measurement data will be reported in weeks or months.
Time frame: Up to approximately 24 months.
duration of response (DOR)
The time from the first documentation of objective tumor response (CR or PR) to the first documented disease progression (assessed per RECIST v1.1) or death from any cause. Measurement data will be reported in weeks or months.
Time frame: Up to approximately 24 months.