CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* 1\. Subjects voluntarily participate in clinical research and sign informed consent.
* 2\. Subjects with CD19-negative relapsed or refractory B-cell lymphoma: a) failure to achieve CR after 6 cycles, or PR after 3 cycles, of first-line therapy, or achieve CR after first-line therapy but relapse within 12 months; b) achieve CR after systemic treatment, but are refractory or relapsed, and no plan to transplant, or prepare for transplantation but cannot meet transplantation criteria after second-line therapy; c) not achieve CR after at least two courses of second-line treatment (including autologous stem cell transplantation).
* 3\. Expected survival ≥ 3 months.
* 4\. BAFF-R expression are detected on tumor cells of subjects by flow cytometry or immunohistochemistry.
* 5\. ECOG score ≤ 2.
* 6\. Subjects with adequate organ functions prior to enrollment, meet the following laboratory values:
* Renal function: serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m²
* Hepatic function: Serum alanine aminotransferase (ALT) ≤ 5 × age-specific ULN and total bilirubin ≤ 2.0 mg/dL, except in subjects with Gilbert-Meulengracht syndrome. If total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN, subjects with Gilbert-Meulengracht syndrome are included.
* Pulmonary reserve: ≤ Grade 1 dyspnea and oxygen saturation \>95% on room air.
* 7\. Stable hemodynamics and left ventricular ejection fraction (LVEF) ≥ 45 % assessed by echocardiography or multi-gated radionuclide angiography (MUGA).
* 8\. Adequate bone-marrow reserve without blood transfusion as defined by:
* Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L.
* Absolute lymphocyte count (ALC) ≥ 0.1 x 10\^9/L.
* Platelets ≥ 50 x 10\^9/L.
* Hemoglobin \>80g/L.
* 9\. In the investigator's judgment, subjects' general condition and all biochemical values are either normal or sufficiently compensated to receive lymphodepletion and CAR-T cell therapy.

Exclusion Criteria:

* 1\. Women who are pregnant or breastfeeding, or planned pregnancy within 6 months.
* 2\. Infectious disease(HIV, Active Tuberculosis ect.).
* 3\. Active infection: hepatitis B, hepatitis C.
* 4\. Abnormal vital signs or refuse to receive examination.
* 5\. Subjects with psychiatric or psychological disorders are unable to complete treatment or efficacy assessment.
* 6\. History of severe hypersensitivity or known hypersensitivity to IL-2.
* 7\. Systemic or local severe infection requiring antimicrobial therapy.
* 8\. Significant dysfunction of vital organs (heart, lung, brain, kidney, etc.), or in the investigator's judgment, subjects are unable to be enrolled with any other condition.

主要终点：Incidence of dose-limiting toxicity (DLT) · Dose-limiting toxicity for each subject · 1 month after injection；AE/SAE · Incidence and severity of adverse events (AE), and serious adverse event (SAE) · 1 month, 3 months, 6 months, 12 months after injection
次要终点：Objective response rate (ORR)；Overall survival (OS)；Duration of response (DOR)；Progression-free survival (PFS)

• BAFF-R CAR-T Cells treatment arm · EXPERIMENTAL · Subjects will be administrated with BAFF-R CAR-T Cells after lymphocyte depletion by fludarabine and cyclophosphamide.

The purpose of this study is to evaluate the safety and tolerability of BAFF-R CAR-T Cells in Adult Subjects with CD19-Negative relapsed or refractory B-Cell Lymphoma.