Cord Blood-derived CAR-NK Cells Targeting CD19 for Refractory/Relapsed Central Nervous System Lymphoma

Korábbi kezelés

• 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.

• 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;