A study of chimeric antigen receptor T lymphocytes (CAR-T) in the treatment of relapsed and refractory non-Hodgkin lymphoma

This is a single-center, single-arm, open-label study. After meeting the eligibility criteria and enrolling on the trial, patients will undergo leukapheresis for collection of autologous lymphocytes. Once cells have been manufactured, patients will then proceed to lymphodepleting chemotherapy with cyclophosphamide and fludarabine for 1-2 consecutive days followed by the infusion of CAR T-cells at a target dose of 3-10×105 cells/kg.

Inclusion Criteria:

1. CD19-positive non-Hodgkin lymphoma confirmed by cytology or histology according to WHO2016 criteria:
3. Age ≥18 years old (including the threshold);
4. According to the 2014 version of Lugano criteria, there is at least one two-dimensional measurable lesion as the evaluation basis: for intranodal lesions, it is defined as: long diameter >1.5cm; for extranodal lesions, long diameter should be >1.0cm;
5. Eastern Cooperative Oncology Group activity status score ECOG score 0-2;
6. The venous access required for collection can be established, and there are enough cells collected by non-mobilized apheresis for CAR-T cell production;
7. Liver and kidney function, cardiopulmonary function meet the following requirements:
9. Be able to understand and voluntarily sign the informed consent.

Exclusion Criteria:

1. Received CAR-T therapy or other gene-modified cell therapy before screening;
2. Received anti-tumor therapy (except systemic immune checkpoint inhibition or stimulation therapy) within 2 weeks or 5 half-lives (whichever is shorter) before screening. 3 half-lives are required to enroll (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 receptor agonist, 4-1BB receptor agonist, etc.);
3. Those who have received hematopoietic stem cell transplantation (ASCT) within 12 weeks before apheresis, or who have previously received allogeneic hematopoietic stem cell transplantation (HSCT), or those who have solid organ transplantation; immunosuppression is required within 2 weeks before apheresis Grade 2 and above GVHD of the drug;
4. Patients with atrial or ventricular lymphoma involvement or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression;
5. Have been vaccinated with live attenuated vaccine within 6 weeks before clearing the leprosy;
6. Cerebrovascular accident or epilepsy occurred within 6 months before signing the ICF;
7. History of myocardial infarction, cardiac bypass or stent, unstable angina or other clinically significant heart disease within 12 months prior to signing the ICF;
8. Active or uncontrolled autoimmune diseases (such as Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus), except those that do not require systemic treatment;
9. Malignant tumors other than non-Hodgkin lymphoma within 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, Ductal carcinoma in situ;
10. Uncontrollable infection within 1 week before screening;
11. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is greater than the normal reference range; or hepatitis C virus (HCV) antibody positive and peripheral blood C Hepatitis virus (HCV) RNA titer test is greater than the normal reference range; or human immunodeficiency virus (HIV) antibody positive; or syphilis test positive; cytomegalovirus (CMV) DNA test positive;
12. Women who are pregnant or breastfeeding; or women of childbearing age who have a positive pregnancy test during the screening period; or male or female patients who are unwilling to use contraception from the time of signing the informed consent form to 1 year after receiving CAR-T cell infusion;
13. Other investigators deem it inappropriate to participate in the study.