Clinical Study of Multi-targeted CAR-T Therapy in Patients With Relapsed/Refractory B-Cell Lymphoma

Inclusion Criteria19

• Voluntary written informed consent obtained from the participant (or legally authorized representative) with good compliance expected throughout the study.
• All of the following must be fulfilled:
• Age 2-75 years at the time of informed consent; both sexes eligible.For minors (≤18 years), consent must be provided by a parent or legal guardian; minors who are able to sign must co-sign with their guardian.
• Histologically confirmed B-cell lymphoma according to the NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (2024 v3).
• Relapsed or refractory B-cell lymphoma after at least two prior lines of therapy (one standard chemo-regimen + one salvage regimen) that must have included:
• anti-CD20 monoclonal antibody (except for subjects with documented CD20-negative tumors), and
• an anthracycline-containing regimen.
• Subjects must additionally meet at least one of the following:
• i. Ineligible for autologous hematopoietic stem-cell transplantation (ASCT); ii. Refusal of ASCT; iii. Relapse after ASCT. d) Disease status at screening:
• • Relapse: progression after prior response (PR or CR).
• • Refractory: i. No response to last therapy (progressive disease \[PD\] during/after, or best response ≤SD lasting \<6 months); OR ii. Relapse or progression after ASCT (biopsy-proven) including: relapse/PD ≤12 months post-ASCT, or relapse/PD after salvage therapy post-ASCT without response (SD or PD).
• Tumor tissue (archival or fresh biopsy) positive for CD20 and/or CD19 and/or CD22 by immunohistochemistry (pathology report within 6 months preferred).
• ≥1 measurable lesion per Lugano 2014 (Cheson) criteria.
• ECOG performance status 0-3.
• Adequate marrow reserve at screening:Absolute lymphocyte count (ALC) ≥0.3 × 10⁹/L; Platelets ≥30 × 10⁹/L (transfusion permitted).
• Adequate organ function:AST ≤3×ULN (≤5×ULN if attributable to tumor infiltration); ALT ≤3×ULN (≤5×ULN if attributable to tumor infiltration); Total bilirubin ≤2×ULN (≤3×ULN with direct bilirubin ≤1.5×ULN for Gilbert's syndrome); Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault); Pulmonary reserve: ≤Grade 1 dyspnea and SpO₂ \>91 % on room air; LVEF ≥50 % by echocardiography; INR ≤1.5×ULN and APTT ≤1.5×ULN.
• Women of child-bearing potential must have a negative serum/urine pregnancy test within 7 days before CAR-T infusion. All participants with reproductive potential must use effective contraception from screening through at least 12 months after the last CAR-T dose.
• Adequate venous access for leukapheresis or repeated phlebotomy, with no contraindications to leukapheresis.
• Anticipated survival ≥3 months.