| Eligibility |
Inclusion Criteria:
1. Willing to participate in this clinical study and sign an informed consent form;
2. Age = 18 years old;
3. Estimated survival time = 3 months;
4. Presence of at least one measurable lesion as assessed according to Lugano
Classification 2014 for response assessment in lymphomas (i.e., the cross-sectional
images obtained by CT show that the long diameter of lymph node lesions is > 15 mm or
the long diameter of extranodal lesions is > 10 mm, and FDG-PET scan results are
positive). Lesions, for which radiotherapy was provided, can be regarded as measurable
lesions only if there is an unequivocal progression after radiotherapy;
5. Histopathologically confirmed aggressive B-NHL; positive expression of CD19 in tumors
detected by immunohistochemistry or flow cytometry; pathological types of B-NHL
(according to WHO Lymphoma Classification 2016);
6. Relapsed or refractory diseases;
7. Subjects who must receive adequate prior therapy;
8. Absence of invasion of central nervous system (CNS) lymphoma by cranial magnetic
resonance imaging (MRI);
9. Hematological parameters meeting the requirements;
10. Blood biochemistry meeting the requirements;
11. LVEF = 55%;
12. No severe pulmonary disorders;
13. Toxic reactions induced by prior anti-lymphoma therapy must be stable and resolved to
grade = 1;
14. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
15. Patients with physical conditions for apheresis of peripheral blood; 16 . Willing to
abide by the rules formulated in the study protocol.
Exclusion Criteria:
1. Pregnant or lactating women;
2. Subjects who previously received allogeneic cell therapies, including allogeneic stem
cell transplant;
3. Subjects who previously received anti-CD19 targeted therapy, except those who receive
BRL-201 and are eligible to receive reinfusion in this study;
4. Prior treatment with any CAR-T cell product or other genetically modified T cell
therapies;
5. History of Richter's transformation of chronic lymphocytic leukemia (CLL);
6. Presence of uncontrollable fungal, bacterial, viral, or other infections requiring
systemic therapy. Patients can be enrolled if the simple urinary tract infection or
pharyngitis responds to treatment;
7. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core
antibody (HBcAb) and peripheral blood HBV DNA titer higher than the upper limit of
detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA
positive; human immunodeficiency virus (HIV) antibody positive; syphilis test
positive;
8. Severe mental disorders; history of CNS disorders (e.g., epileptic seizure,
cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any
CNS-involved autoimmune disorders);
9. Active autoimmune disorders requiring immunotherapy, including but not limited to end
organ damages caused by autoimmune disorders (e.g., Crohn's disease, rheumatoid
arthritis, and systemic lupus erythematosus) in the past 2 years, or requiring
systemic application of immunosuppressive drugs or other drugs for systemic control of
diseases;
10. Primary immunodeficiency;
11. History of other malignancies;
12. Patients with severe cardiovascular disorders, including but not limited to those with
lymphoma infiltration in the cardiac atrium or ventricles and those with a history of
myocardial infarction, cardioangioplasty or stent implantation, unstable angina, or
other clinically significant heart diseases within 12 months before enrollment;
13. History of deep venous thrombosis or pulmonary embolism within 6 months before
enrollment;
14. Patients who are receiving oral anticoagulant therapy; prothrombin time (PT),
activated partial thromboplastin time (APTT), or international normalized ratio (INR)
> 1.5 × ULN without anticoagulant therapy;
15. Presence of any indwelling tube or catheter (e.g., tube or catheter for percutaneous
nephrostomy, indwelling catheter, or catheter in pleural cavity/peritoneal
cavity/pericardium). Dedicated central venous access catheters (e.g., Port-a-Cath or
Hickman catheter) are permitted;
16. Lymphoma cells detected in cerebrospinal fluid, presence of brain metastases, history
of CNS lymphoma, or history of lymphoma cells detected in cerebrospinal fluid or brain
metastases;
17. Conditions (e.g., intestinal obstruction or vascular compression) requiring emergency
treatment due to tumor masses;
18. History of severe immediate hypersensitivity to any drug to be used in this study;
19. Vaccination of live vaccines, excluding corona virus disease 2019 (COVID-19) vaccines,
within = 6 weeks before the start of the pretreatment regimen;
20. Any circumstances that possibly increase the risk of subjects or interfere with the
study results as judged by the investigator.
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