A Clinical Study on the Safety of in Vivo- CAR-T Cell Immunotherapy Targeting CD19/CD20 for the Treatment of Relapsed/Refractory B-cell Lymphoma
This Phase 1, open-label, single-arm, dose-escalation study is designed to evaluate the safety and tolerability of SL1617 Injection in patients with relapsed or refractory B-cell lymphoma. SL1617 is an investigational in vivo CAR T-cell immunotherapy targeting CD19 and CD20, utilizing an engineered lentiviral vector to generate functional CAR-T cells in vivo without the need for ex vivo cell processing or lymphodepletion. Participants will receive a single intravenous infusion of SL1617 using a traditional 3+3 dose-escalation design. The planned starting dose is 1.0 × 10\^9 transducing units (TU), followed by dose levels of 3.0 × 10\^9 TU and 6.0 × 10\^9 TU. Dose escalation will be guided by the occurrence of dose-limiting toxicities (DLTs).
• 1\. The subject voluntarily agrees to participate in the study, has signed the informed consent form, and is willing and able to comply with the scheduled visits, study treatment, laboratory tests, and other study procedures.
• 2\. Patients with B-cell lymphoma confirmed by cytological or histopathological examination according to the 2022 World Health Organization classification, meeting all of the following criteria:
⁃ Lymphoma cells are confirmed to express CD19 and/or CD20 antigens by immunophenotyping or immunohistochemical examination.
⁃ Eligible B-cell lymphomas include:
∙ Aggressive B-cell lymphomas, including large B-cell lymphoma (LBCL), Burkitt lymphoma (BL), and mantle cell lymphoma (MCL);
‣ Indolent B-cell lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), and hairy cell leukemia (HCL).
⁃ Relapsed or refractory B-cell lymphoma, defined as follows:
∙ Relapse: The patient has received adequate prior therapy and previously achieved a complete response (CR) or partial response (PR) after first-line systemic therapy (which must include an anti-CD20 monoclonal antibody and an anthracycline-containing chemotherapy regimen), second-line or subsequent systemic therapy, or autologous hematopoietic stem cell transplantation (ASCT), but relapsed after the completion of treatment, with disease progression confirmed by cytology or histology;
‣ Refractory: The patient failed to achieve CR or PR after first-line systemic therapy, or had no response to the most recent second-line or subsequent systemic therapy regimen, with progressive disease (PD) or stable disease (SD) as a best response of treatment.
⁃ The patient must have at least one measurable lesion. If salvage therapy was administered after ASCT, the patient must have no response to the most recent salvage therapy or must have relapsed after the most recent salvage therapy. Patients with relapsed indolent lymphoma may be enrolled only if clinical indications for treatment are present, such as symptomatic mass lesions, organ compression, cytopenias, or B symptoms.
• 3\. Male or female subjects aged 18-75 years, inclusive. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. Estimated life expectancy of more than 3 months from the date of signing the informed consent form.
• 6\. Absolute neutrophil count≥1×10\^9/L, platelet count≥75×10\^9/L, hemoglobin≥60g/L.
• 7\. Adequate renal, hepatic, cardiac, and pulmonary function, defined as follows:
⁃ Creatinine clearance (estimated by the Cockcroft-Gault formula) ≥60 mL/min;
⁃ Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×upper limit of normal (ULN), total bilirubin≤1.5×ULN;
⁃ Cardiac ejection fraction≥50%, no pericardial effusion on echocardiography, and no significant abnormalities on electrocardiogram (ECG);
⁃ No clinically significant pleural effusion, and oxygen saturation \>92% on room air at baseline.
• 8\. Subjects agree to use effective contraception from the time of signing the informed consent form until 1 year after cell infusion.