Tests CD19-targeted immune cells for lymphoma in the brain or spinal cord

Trial details

Who runs it

Second Affiliated Hospital, Zhejiang University, School of Medicine

Trial code

NCT06827782

Record updated

15 August 2025

Original description

This study is designed to evaluate the safety and efficacy of cord blood-derived CAR-NK019 in the treatment of refractory/relapsed central nervous system lymphoma.Read full original descriptionShow less

Clinical Study of Cord Blood-derived CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed Central Nervous System Lymphoma

This study is designed to evaluate the safety and efficacy of cord blood-derived CAR-NK019 in the treatment of refractory/relapsed central nervous system lymphoma.

Inclusion: Patients with refractory/recurrent CNS lymphoma must meet all of the following criteria to be eligible:; Voluntarily participate in the study and sign the informed consent; Age 18-75 years old, male or female; Diffuse large B-cell lymphoma (DLBCL) was confirmed by histology. CD19 expression was positive by lymphoma pathology or flow cytometry, and CD19 expression was ≥20% by IHC; Imaging showed no evidence of systemic lymphoma; Meets any of the following definitions for refractory/relapsed CNS lymphoma: no complete response has been achieved with prior 2-line regimen including methotrexate or cytarabine-based regimen; Disease progression during any treatment; The stable time of disease after effective treatment is less than 6 months; Disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; Imaging showed the presence of at least one measurable lesion, with a minimum diameter of ≥10mm; Expected survival ≥3 months; ECOG score 0-3 points; Adequate organ function reserve:; alanine aminotransferase, ASpartate aminotransferase ≤ 2.5× UNL (upper limit of normal); Creatinine clearance (Cockcroft-Gault method) ≥60 mL/min; Serum total bilirubin and alkaline phosphatase ≤1.5× UNL; Glomerular filtration rate >50ml/min; cardiac ejection fraction (EF) ≥45%; Basic oxygen saturation >92% in indoor natural air environment; Blood routine: absolute number of neutrophils >×109/L, platelet count 45×109/L, hemoglobin 80g/L; Previous autologous hematopoietic stem cell transplantation is allowed, and the interval between stem cell transfusion and CAR-NK transfusion is ≥3 months; Previous CAR-T cell therapy is allowed, and the time interval between CAR-T transfusion and CAR-NK transfusion is ≥3 months; Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraception during the test; Approved anti-tumor therapies, such as systemic chemotherapy, whole body radiotherapy and immunotherapy, have been discontinued for at least 3 weeks before the study; Discontinuation of targeted drug regiments without chemotherapy for at least 2 weeks.

Exclusion: Subjects who meet any of the following criteria will not be admitted to the study:; Allergic to any of the components of cell products; History of other tumors; Acute grade II-IV (Glucksberg standard) GvHD or generalized chronic GvHD occurred after previous allogeneic hematopoietic stem cell transplantation; Or are receiving anti-GVHD treatment; Have received gene therapy within the past 3 months; Active infections requiring treatment (except simple urinary tract infections, bacterial pharyngitis), but prophylactic antibiotic, antiviral and antifungal infection treatment is permitted; Persons infected with hepatitis B (HBsAg positive, but HBV-DNA<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons; Subjects with Grade III or IV cardiac dysfunction according to the New York Heart Association's cardiac function grading criteria; Patients who received antitumor therapy in the early stage but did not recover toxicity (CTCAE 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia); Previous history of epilepsy, autoimmune encephalitis, cerebral infarction or cerebral hemorrhage within 6 months; Whole-body enhanced CT or PET/CT suggests evidence of systemic lymphoma; Lactating women who are unwilling to stop breastfeeding; Any other circumstances that the investigator believes may increase the risk to the subject or interfere with the test results; Patients requiring more than 10mg of dexamethasone per day for 3 days prior to enrollment; Patients who cannot tolerate ommaya capsule implantation; Those who cannot tolerate enhanced magnetic resonance imaging.

ClinicalTrials.gov NCT06827782