Written informed consent: Signed written informed consent and ability to comply with protocol-specified visits and procedures.
Age and life expectancy: Age ≥ 18 years with an expected survival of more than 3 months.
Pathological diagnosis: Histopathologically confirmed CD20+ relapsed or refractory B-cell non-Hodgkin lymphoma (according to WHO 2016 lymphoma classification), including but not limited to:
Relapsed or refractory disease: Defined by meeting one or more of the following:
Relapse, non-response, or progression after hematopoietic stem cell transplantation Stable disease for ≤ 6 months after at least two cycles of second-line therapy (DLBCL/HGBCL/3b FL subtypes must have received CD20-targeted agents and anthracyclines; other subtypes evaluated by investigator for treatment adequacy) Disease progression or relapse after at least second-line therapy (DLBCL/HGBCL/3b FL subtypes must have received CD20-targeted agents and anthracyclines; other subtypes evaluated by investigator for treatment adequacy) ECOG performance status: 0-2.
Contraception requirements:
Fertile males and females of childbearing potential must agree to use effective contraception from signing informed consent until 6 months after last study drug administration Negative serum pregnancy test required for females of childbearing potential at screening
Measurable disease: At least one measurable lesion according to Lugano 2014 criteria:
Lymph node lesions \> 15mm in longest diameter on CT Extranodal lesions \> 10mm in longest diameter FDG-PET positive (SUV ≥ 4 or 5) Radiated lesions only considered measurable if progression documented after completion of radiotherapy
Hematological parameters (no blood transfusion or hematopoietic growth factor within 7 days prior to testing):
International Normalized Ratio (INR) ≤ 1.5×ULN Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN (INR 2.0-3.0 acceptable for subjects on prophylactic anticoagulation)
Organ function requirements:
Renal: Serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula) Hepatic: Total bilirubin ≤ 1.5×ULN (≤ 3×ULN for liver infiltration or Gilbert's syndrome); ALT and AST ≤ 3×ULN (≤ 5×ULN for liver infiltration) Pulmonary: Oxygen saturation ≥ 92% on room air Subjects failing to meet any of the above criteria will not be eligible for enrollment.
You may not be if
Primary CNS involvement: Primary central nervous system lymphoma or active CNS involvement/symptoms.
Severe cardiac rhythm/conduction abnormalities requiring intervention QTcF prolongation (\> 450 ms males, \> 470 ms females) Acute coronary syndrome, heart failure, aortic dissection, stroke, or other ≥ grade 3 cardiovascular events within 6 months NYHA class ≥ II heart failure or LVEF \< 50% Uncontrolled hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 100 mmHg despite medication)
Prior cell therapies/transplants:
Autologous stem cell transplant or cell therapy within 3 months Allogeneic stem cell transplant or cell therapy within 6 months History of solid organ transplantation Prior anticancer therapy: Anticancer treatment or participation in other interventional clinical studies within 4 weeks or 5 half-lives (whichever is shorter) before lymphodepletion.
Recent procedures/vaccinations: Live attenuated vaccine or major surgery within 4 weeks before lymphodepletion, or planned during study.
Systemic steroids: Requirement for prolonged (≥ 3 days) systemic steroid therapy (≥ 10 mg/day prednisone equivalent) during study (inhaled or topical steroids excluded).
Other malignancies/conditions: History of other malignancies (except cured in-situ cervical cancer, non-invasive skin cancers, or locally treated prostate/breast carcinoma with ≥ 2 years remission); severe diabetes or other serious comorbidities.
Active infections: Active fungal, bacterial, viral, or mycobacterial infections requiring systemic treatment within 14 days before lymphodepletion.
Infectious diseases:
HBsAg positive or HBcAb positive with detectable HBV DNA HCV antibody positive with detectable HCV RNA HIV antibody positive Active syphilis Hypersensitivity: Life-threatening hypersensitivity or intolerance to study medications or severe allergic diathesis.
Pregnancy/lactation: Pregnant or breastfeeding females. Other factors: Any condition deemed by investigator to affect compliance or make subject unsuitable for study participation.
Clareo Health | Clinical Study on the Safety and Efficacy of CD20/CD19 Cell Injection in the Treatment of Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
