CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Voluntarily participate in this study and sign the informed consent form.
2. Age range: 18 - 75 years old. Gender is not restricted.
3. Histologically confirmed large B-cell lymphoma, including: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), and mantle cell lymphoma (MCL).
4. CD19-positive (as determined by immunohistochemistry or flow cytometry; based on the most recent tumor biopsy results).
5. Definition of relapsed/refractory: Failure to achieve complete remission (CR) after at least two lines of therapy (which must include a CD20 monoclonal antibody and an anthracycline); or disease progression during any course of treatment; or relapse/progression within 12 months after autologous hematopoietic stem cell transplantation.
6. At least one measurable lesion: any lymph node lesion with a longest dimension \>1.5 cm, or any extranodal lesion with a longest dimension \>1.0 cm, and the lesion shows uptake on PET-CT (SUV greater than the hepatic pool).
7. Absolute neutrophil count in peripheral blood ≥ 1,000/μL; platelet count ≥ 45,000/μL.
8. Cardiac, hepatic, and renal function: creatinine \< 1.5 mg/dL; ALT/AST ≤ 2.5 times the upper limit of normal; total bilirubin \< 1.5 mg/dL; ejection fraction ≥ 50%.
9. Possess sufficient cognitive capacity to voluntarily sign the informed consent form.
10. Participants of reproductive potential must be willing to use effective contraception (from the time of signing the informed consent form until 12 months after CAR-T infusion).
11. The investigator estimates a life expectancy of at least 4 months.
12. Willing to comply with the schedule of visits, dosing regimen, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. History of other malignant tumors (excluding cured basal cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc.).
2. Autologous hematopoietic stem cell transplantation within the past 6 weeks.
3. Any targeted CAR-T therapy within 3 months prior to this CAR-T treatment.
4. Patients who have previously received PD-1 monoclonal antibodies must have a washout period of ≥3 months before enrollment.
5. Received cytotoxic drugs, glucocorticoids (except for prednisone-equivalent doses of ≤10 mg/day), or other targeted therapies within 2 weeks prior to cell collection.
6. Active autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease, etc.).
7. Uncontrolled active bacterial, fungal, or viral infections.
8. HIV infection, syphilis; active hepatitis B or C: Hepatitis B: HBsAg-positive and HBV-DNA ≥ 1,000 IU/mL; Hepatitis C: HCV RNA-positive and abnormal liver function.
9. Known central nervous system lymphoma (confirmed by brain MRI or CT and cerebrospinal fluid examination).

主要终点：Determination of the Recommended Phase II Dose (RP2D) · Based on the incidence of DLTs, CAR-T cell kinetics, preliminary efficacy, and safety data from the Phase Ib dose-escalation phase, the Safety Review Committee (SRC) determined the RP2D following a comprehensive evaluation. · Up to 3 months；Objective Response Rate (ORR) · At 3 months (±7 days) after infusion, the proportion of patients achieving complete remission (CR) or partial remission (PR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort. · Up to 3 months；Complete Remission Rate (CR Rate) · At 3 months (±7 days) after infusion, the proportion of patients who achieved complete remission (CR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort. · Up to 3 months
次要终点：Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria；Incidence and duration of Grade ≥3 hematologic toxicities assessed according to CTCAE version 5.0；Incidence of clinically significant infections requiring anti-infective treatment or hospitalization；Progression-Free Survival (PFS)；Overall Survival (OS)；Duration of Response (DOR)；In Vivo Kinetics of CAR-T Cells；Serum Cytokine Dynamics

• 7×19-THEMIS CAR-T · EXPERIMENTAL · A single dose intravenous injection of 7X19-Themis at day 0

This study is aimed to explored the safety and efficacy of 7×19-THEMIS CAR-T cell therapy for large B-cell lymphoma and to conduct an exploratory comparison of the 3-month objective response rate (ORR) and complete remission rate (CR rate) between the experimental cohort and the historical control cohort (NCT04833504).