Safety, Efficacy and Pharmacokinetics of XKDCT023 in DLBCL

Inclusion Criteria:

• All subjects or legal guardians must sign the informed consent approved by the ethics committee in writing before starting any screening procedure.
• Adult patients aged 18 and over with recurrent or refractory DLBCL.
• Bone marrow negative or bone marrow lymphoma cells in screening stage determined by CT scan < 30%.
• The subject had been adequately treated before.
• According to the revised IWG malignant lymphatic efficacy evaluation criteria (2007 Edition), there was at least one measurable lesion in the baseline period.
• Estimated survival ≥ 12 weeks.
• The baseline ECoG score was 0 or 1.
• Adequate organ function.
• Hemodynamics determined by echocardiography or multichannel radionuclide angiography (MUGA) were stable and left ventricular ejection fraction (LVEF) ≥ 45%.
• Sufficient bone marrow reserve without blood transfusion.
• There must be non mobilized apheresis or peripheral blood collected cells for car-t cell production.
• According to the judgment of the researcher, the patient has fully recovered from the toxicity of previous anti-tumor treatment and is suitable for pretreatment chemotherapy and car-t cell treatment.
• Women of childbearing age and all male subjects must agree to use efficient contraceptive methods until at least 12 months after xkdct023 infusion, and until two consecutive PCR tests show that car-t cells are no longer present in the body.

Exclusion Criteria:

• Patients who have previously received any anti-CD19 / anti-CD3 treatment, or any other anti-CD19 treatment;
• Patients previously treated with any gene therapy product, including car-t treatment;
• Patients with detectable cerebrospinal fluid malignant cells or brain metastasis, or patients with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma;
• Patients with testicular invasion, including patients with orchiectomy;
• Patients with current or history of central nervous system diseases, such as epilepsy, cerebrovascular ischemia / hemorrhage, dementia, cerebellar diseases or any autoimmune diseases involving the central nervous system;
• Patients who had previously received allogeneic hematopoietic stem cell transplantation (HSCT);
• Patients who are suitable and willing to receive autologous hematopoietic stem cell transplantation (ASCT);
• The feasibility evaluation screening stage showed that the lymphocyte transfection efficiency of patients was less than 5%, or patients whose T cell culture could not be expanded (< 5 times).
• Patients who received chemotherapy other than lymphocyte clearance chemotherapy within 2 weeks before xkdct023 infusion;
• Patients who had received other study drugs within 30 days before screening;
• Patients who received radiotherapy within 2 weeks before infusion;
• Active hepatitis B (defined as hepatitis B virus DNA detection value > 1000 copies/ml) or hepatitis C virus (HCV RNA positive) patients.
• HIV positive or Treponema pallidum positive patients;
• Patients with acute life-threatening bacterial, viral or fungal infections that have not been controlled (e.g. positive blood culture ≤ 72 hours before infusion);
• Patients with unstable angina pectoris and / or myocardial infarction within 6 months before screening;
• Patients with previous or concurrent malignancies, with the following exceptions: well treated basal cell or squamous cell carcinoma (sufficient wound healing is required before enrollment in the study); Cervical cancer or breast cancer in situ cancer, after curable treatment, had no recurrence at least 3 years before the study. The primary malignant tumor has been completely removed and completely relieved for ≥ 5 years.
• Pregnant or lactating female patients (women of childbearing age are verified as positive results by serum or urine pregnancy test during the screening period);
• There are arrhythmia patients without medical management control;
• Patients who received oral anticoagulant therapy within 1 week before car-t cell infusion;
• Patients who had previously received any adoptive T cell therapy;
• active neuroautoimmune or inflammatory disorders (e.g. Guillian Barre syndrome, amyotrophic lateral sclerosis).