This study is to investigate the safety and tolerability of C402-CD19-CAR treatment in subjects with relapsed or refractory large B-cell lymphoma and further determine the recommended Phase 2 dose of C402-CD19-CAR.
Male or female 18-75 years (inclusive);
Patients can understand this study and capable of providing informed consent;
Patients with willingness to be in the study and comply with the study visit procedures and other protocol requirements;
Diagnosed with CD19-positive large B-cell lymphoma (LBCL) based on cytology or histology according to the WHO 2016 standards, including diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS), grade 3b follicular lymphoma (FL), transformed diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBL), high-grade B-cell lymphoma (HGBL) with MYC, BCL-2, and/or BCL-6 rearrangements, and high-grade B-cell lymphoma not otherwise specified (HGBL-NOS). For CD19 expression status, subjects with a clear past record of tumor histological diagnosis as CD19-positive (within 6 months prior to screening with no CD19-related treatment in the last 6 months) and tumors showing CD19-positive lymphoma levels ≥ 50% by IHC or CD19-positive lymphoma levels ≥ 70% by flow cytometry. If there is no previous CD19 tumor testing or the result is over 6 months prior to screening, a new tumor pathology sample must be provided or re-collected for CD19-positive diagnosis by the institution, with IHC showing CD19-positive lymphoma levels ≥ 50% or flow cytometry showing CD19-positive lymphoma levels ≥ 70%.
History of receiving allogeneic hematopoietic stem cell transplantation, adoptive cell therapy (such as CAR-T therapy), or other gene-modified cell therapies;
Any active central nervous system (CNS) involvement (including symptomatic and asymptomatic), or a history of CNS disease (such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disorders, or any autoimmune diseases involving the CNS);
Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA positivity, or subjects with HBV titers above the upper limit of the normal range for the study center; positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA positivity; positive for cytomegalovirus (CMV) DNA; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis test;
Any unstable systemic disease, including but not limited to unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ III), active bleeding, severe arrhythmias requiring drug treatment, liver, kidney, or metabolic disorders;
Shanghai Exuma Biotechnology Ltd.
Lead sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborator