Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Key Inclusion Criteria: Patients who are willing to sign the informed consent form; Aged 18-75 years, male or female; Previously received≥2nd-line adequate therapy or hematopoietic stem cell transplantation (HSCT), and patients with CD19+/CD22+ relapsed/refractory B-NHL according to the WHO classification 2017, which are provided specifically as follows: Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS); Primary mediastinal large B cell lymphoma (PMBCL); Grade 3b follicular lymphoma; Transformed follicular lymphoma; High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high grade B cell lymphoma - not otherwise specified. Measurable imaging lesion at screening: Intranodal lesion must have a long diameter of more than 1.5 cm, and extranodal lesion must have a long diameter of more than 1.0 cm with PET-positive disease by Lugano classification . PET-positive disease BY Lugano classification Adequate bone marrow, renal, hepatic, pulmonary and cardiac function. Adequate vascular access for leukapheresis procedure Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy. Key Exclusion Criteria: Active Central Nervous System (CNS) involvement by malignancy. Patients with existing central nervous system disease or with a history of central nervous system disease. Patients receiving any of the following drugs or therapies within the specified period prior to apheresis: Alemtuzumab and Bendamustine within 6 months prior to apheresis; Cladribine within 3 months prior to apheresis; Lenalidomide within 1 mouth prior to apheresis; Lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible; Anti-CD20 monoclonal antibody and therapeutic dose of hormones within 7 d prior to apheresis; Non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible; Venetoclax (BCL-2 inhibitor) within 4 d prior to apheresis; Idelalisib (PI3Kδ kinase inhibitor) within 2 d prior to apheresis; DLI within 6 weeks prior to apheresis; Radiotherapy within 6 weeks prior to apheresis - progressive disease at radiotherapy site, or PET positive lesion at other non-radiotherapy site is eligible; Patients previously received CAR-T cell therapy, the products that have same indication and have beenlisted in China are eligible; Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 mouths. Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening. Active systemic autoimmune disease. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive). Patients with active infections at screening. History of cardiovascular disease. Pregnant or nursing women.