A Phase Ib/II Exploratory Clinical Trial of Memory-Enhanced 7×19-THEMIS CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma

Prior treatment

• Autologous hematopoietic stem cell transplantation within the past 6 weeks.
• Any targeted CAR-T therapy within 3 months prior to this CAR-T treatment.
• Patients who have previously received PD-1 monoclonal antibodies must have a washout period of ≥3 months before enrollment.
• Received cytotoxic drugs, glucocorticoids (except for prednisone-equivalent doses of ≤10 mg/day), or other targeted therapies within 2 weeks prior to cell collection.

Other illness

• History of other malignant tumors (excluding cured basal cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc.).
• Active autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease, etc.).
• Uncontrolled active bacterial, fungal, or viral infections.
• 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.

Other

• Known central nervous system lymphoma (confirmed by brain MRI or CT and cerebrospinal fluid examination).

• Voluntarily participate in this study and sign the informed consent form.
• Age range: 18 - 75 years old. Gender is not restricted.
• 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).
• CD19-positive (as determined by immunohistochemistry or flow cytometry; based on the most recent tumor biopsy results).
• 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.
• 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).
• Absolute neutrophil count in peripheral blood ≥ 1,000/μL; platelet count ≥ 45,000/μL.
• 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%.
• Possess sufficient cognitive capacity to voluntarily sign the informed consent form.
• 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).
• The investigator estimates a life expectancy of at least 4 months.
• Willing to comply with the schedule of visits, dosing regimen, laboratory tests, and other trial procedures.