Clinical Study on the Safety and Efficacy of CD20/CD19 Cell Injection in the Treatment of Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Overview

Evaluate the safety and tolerability of AcNK-Sup003 cell injection in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). To preliminarily determine the Maximum Tolerated Dose (MTD) or recommended clinical dose of AcNK-Sup003 cell injection.

Interventions

• Drug AcNK-Sup003 cell injection
  AcNK-Sup003 cell injection in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL)

Primary outcome measures

• Overall survival [Time frame: Time frame:1, 3,6,12,18, 24 months after treatment]

Eligibility criteria

Inclusion criteria

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:

Diffuse large B-cell lymphoma (DLBCL) High-grade B-cell lymphoma (HGBCL) Follicular lymphoma grade 3b (3b FL)

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):

Hemoglobin (Hb) ≥ 80 g/L Absolute neutrophil count (ANC) ≥ 1×10⁹/L Platelet count (PLT) ≥ 50×10⁹/L

Coagulation function:

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.

Exclusion criteria

Primary CNS involvement: Primary central nervous system lymphoma or active CNS involvement/symptoms.

Autoimmune conditions: Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, autoimmune thrombocytopenia) or uncontrolled pleural effusions.

Cardiovascular history:

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and — Wuhan

Identifiers

NCT: NCT07345741 · DHZ1962-E

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗