CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Informed Consent: Signed informed consent by the participant or legally authorized representative.
2. Age \& Performance Status:

   * Age ≥ 18 years
   * ECOG performance status ≤ 2
3. Diagnosis \& Disease Criteria:

   * Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
   * BAFF-R expression on lymphoma cells required.
4. Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
5. Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence \< 5% before leukapheresis.
6. Organ Function \& Laboratory Criteria:

   * Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
   * Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT \< 3x ULN.
   * Renal Function: CrCl ≥ 50 mL/min.
   * Cardiac \& Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation \> 91% on room air.
7. Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
8. Reproductive Considerations:

   * Negative pregnancy test for females of childbearing potential.
   * Use of effective contraception or abstinence through 3 months post-treatment.

Exclusion Criteria:

1. Prior Therapies \& Transplants:

   * Prior allogeneic SCT.
   * Autologous SCT \< 6 months before leukapheresis.
   * Concurrent systemic steroids or chronic immunosuppressant use.
2. Disease-Specific Exclusions:

   * Cardiac lymphoma involvement.
   * Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
3. Medical Conditions:

   * Active autoimmune disease requiring immunosuppressants.
   * Primary immunodeficiency.
   * Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
   * Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
   * History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
   * Uncontrolled systemic infections or active CNS lymphoma.
4. Pregnancy \& Breastfeeding: Females who are pregnant or nursing.
5. Other Considerations:

   * Investigator-determined safety concerns.
   * Potential noncompliance with study procedures.

主要终点：Incidence of adverse events · Assess the safety of administering BAFFR-CAR T cells in participants with relapsed or refractory (r/r) B-cell Non-Hodgkin's Lymphoma (B-NHL) and it's subtypes. Toxicity will be graded per Common Terminology Criteria for Adverse Events version 5.0, Cytokine Release Syndrome (CRS) and neurotoxicity which use the American Society for Transplantation and Cellular Therapy Consensus Criteria (ASTCT) and Graft versus Host Disease (GVHD) criteria. Toxicities will be followed from the start of lymphodepletion until the end of the study. · Up to 1 year post treatment；Maximum Tolerated Dose (MTD) · Determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of BAFFR-CAR T cells. The highest dose with ≤ 1/6 participants with DLT will be considered the MTD. · The DLT evaluation period is defined as 28 days following BAFFR CAR-T infusion.
次要终点：Disease Response；Minimal Residual Disease (MRD)；B Cell Quantification；Progression-free survival (PFS)；Overall Survival (OS)

• B-cell activating factor receptor-Chimeric antigen receptor T cells [BAFFR-CAR T cells] · EXPERIMENTAL · BAFFR-CAR T cells in participants with r/r B-NHL

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)