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;
Single group
C402-CD19-CAR
Biological/VaccineEnrolled subjects will undergo apheresis to acquire peripheral blood mononuclear cells. C402-CD19-CAR will be generated from the subject's autologous T cells modified from the apheresis product. After C402-CD19-CAR production and product release, subjects will be administered with a single dose of C402-CD19-CAR via subcutaneous injection.
MTD (maximum tolerated dose) of C402-CD19-CAR
To evaluate the DLT (dose limiting toxicities), attributed to C402-CD19-CAR per cohort and determine the RP2D (recommended phase 2 dose).
AE (Adverse Event), AESI (Adverse Event of Special Interest), SAE (Severe Adverse Event)
The incidence, severity and duration of AE, AESI and SAE as determined by NCI-CTCAE v5.0
ORR (Objective Response Rate)
ORR and best overall response (BOR) of subjects with PR (partial response) and CR (complete response) as determined by local investigator using Lugano 2014
DOR (Duration of response)
The duration of time from record of response to first progression of disease or death as determined by Lugano 2014
PFS (Progression free survival)
The duration of time from treatment to first progression of disease as determined by Lugano 2014
DCR (Disease control rate)
The proportion of subjects with CR (complete response), PR (partial response) or SD (stable disease lasting over 6 months) to total number of patients treated as determined by local investigator using Lugano 2014
Correlation between PK, cytokine concentration and efficacy
Calculate the correlation between PK data, cytokine concentration with efficacy parameters (PFS, OS, ORR, DCR, DOR)
B cell count
Test B cell count and the subsets percentage in blood before and post C402-CD19-CAR treatment
RCL (replication-competent lentivirus) test
Test VSVG copies/μg gDNA in blood after treatment
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Shanghai Exuma Biotechnology Ltd.
Lead sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborator