CD19-positive hematological malignancies
Conditions
Interventions
Sponsors
Tianjin First Central Hospital
Eligibility
Sex/Gender
All
Age
14 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) All subjects or legal guardians must personally sign the written informed consent form approved by the ethics committee before starting any screening procedure; 2) Patients with B-cell lymphoma between 14 to 75 years old (without boundary value); 3) It meets the clinical criteria for refractory and relapsed B-cell lymphoma. The definition of refractory includes: no response to the latest treatment (the most recent response to the latest treatment is PD; the response to the latest treatment is SD and the maintenance time is not more than 6 months); unsuitable or unwilling to receive autologous stem cell transplantation, or refractory to ASCT. The subject has been fully treated before, and the treatment history includes at least: anti-CD20 monoclonal antibody (rituximab), unless the investigator determines that the tumor is CD20 negative; a chemotherapy regimen containing anthracyclines; according to revision IWG's evaluation criteria for malignant lymphatic efficacy (2007 version), with at least one measurable lesion at baseline; 4) The expected survival period is >= 12 weeks; 5) ECOG (Eastern Cooperative Oncology Group) score at baseline is 0 or 1; 6) Sufficient organ function: Renal function is defined as: plasma creatinine = 60 ml/min/173m2; Liver function is defined as: patients with ALT = 45% as determined by echocardiography or multi-channel radionuclide angiography (MUGA); 8) Sufficient bone marrow reserve without blood transfusion, defined as: absolute neutrophil count (ANC) > 1.000 /mm3; absolute lymphocyte count (ALC) >= 300 /mm3; platelets >= 50.000 /mm3; hemoglobin > 8.0g/dl; 9) Cells collected from non-mobilized apheresis or peripheral blood must be available for CAR-T cell production; 10) Patients who use the following drugs should meet the following conditions: Steroids: The therapeutic dose of steroids must be stopped 2 weeks before CD19+CXCR5 infusion. However, physiological alternative doses of steroids are allowed; Immunosuppression: Any immunosuppressive drugs must be stopped >= 4 weeks before being selected; Anti-proliferative therapy other than lymph wasting chemotherapy within two weeks before infusion; The CD20 antibody-related treatment must be stopped within 4 weeks or 5 half-lives (whichever is longer) before the infusion; CNS disease prevention must be stopped 1 week before CD19+CXCR5 infusion (such as intrathecal methotrexate injection); 11) Women of childbearing age and all male subjects must agree to use high-efficiency contraceptive methods for at least 12 months after CD19+CXCR5 infusion, and until 2 consecutive PCR tests show that there are no CAR-T cells in the body.
Exclusion criteria
Exclusion criteria: 1) Patients who have previously received any anti-CD19/anti-CD3 treatment or any other anti-CD19 treatment; 2) Patients who have received any gene therapy product treatment before, including CAR-T treatment; 3) Patients with detectable cerebrospinal fluid malignant cells or brain metastases, or patients with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma; 4) Patients with testicular invasion, including patients whose testicles have been removed; 5) Patients who are currently suffering from or have a history of central nervous system diseases, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases or any autoimmune diseases involving the central nervous system; 6) Patients who have received chemotherapy other than lymphocyte depletion chemotherapy within 2 weeks before CD19+CXCR5 infusion; 7) Patients who have received other study drug treatment within 30 days before screening; 8) Patients receiving radiotherapy within 2 weeks before infusion; 9) Patients with active hepatitis B (defined as hepatitis B virus DNA test value > 500 IU/mL) or hepatitis C (HCV RNA positive); 10) HIV positive or Treponema pallidum positive patients; 11) Patients with acute life-threatening bacterial, viral or fungal infections that have not been controlled (for example, positive blood cultures = 5 years; 14) Pregnant or lactating female patients; 15) Patients with arrhythmia who have not been controlled by medical management; 16) Patients who received oral anticoagulation therapy within 1 week before CAR-T cell infusion; 17) Patients who have previously received any adoptive T cell therapy; 18) Suffer from active neuroautoimmune or inflammatory conditions (such as Guillian-Barre syndrome, amyotrophic lateral sclerosis); 19) Other conditions that the investigator believes should not participate in this clinical trial, such as poor compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall remission rate;Progression Free Survival; | — |
Countries
China
Contacts
Public ContactZhao Mingfeng
Tianjin First Central Hospital
Outcome results
None listed