Relapsed or refractory acute B-cell lymphoma
Conditions
Interventions
Sponsors
Huizhou Municipal Central Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) All subjects or legal guardians must sign the irB approved informed consent in person before starting any screening procedures; 2) Patients aged 18-75 years (excluding cut-off) with B-cell lymphoma, 3) Meeting the clinical criteria for refractory relapsing B-cell non-Hodgkin's lymphoma, refractory definitions included: no response to the last treatment (recent response to the last treatment regimen was PD; Response to the last treatment was SD and lasted no more than 6 months); Unsuitable or unwilling to undergo autologous stem cell transplantation, or refractory ASCT. The subject has previously been adequately treated with a history of at least: ? monoclonal antibody against CD20 (rituximab) unless the investigator determines that the tumor is CD20 negative; ? a chemotherapy regimen containing anthracyclines; 4) The presence of at least one measurable lesion at baseline according to the revised IWG efficacy evaluation criteria for malignant lymphoma. 5) Estimated survival =12 weeks; 6) ECOG score of 0 or 1 at baseline; 7) Adequate organ function: ? Renal function is defined as: ? plasma creatinine =1.5 times the upper limit of normal value, or; ? estimates the glomerular filtration rate (eGFR) =60 ml/min/173m2; ? Liver function is defined as: ? ALT=5 times the upper limit of the normal value corresponding to age, and. ? bilirubin =2.0 mg/dl in patients, except in patients with Gilbert-Meulengracht syndrome. Bilirubin =3.0 times the upper limit of the positive constant and directly bilirubin =1.5 times the upper limit of the positive constant Patients with Gilbert-Meulengracht syndrome can be included. ? Must have a minimum level of lung reserve, defined as = class 1 dyspnea and >91% of pulse oxidation in indoor air; 8) Hemodynamically stable and left ventricular ejection fraction (LVEF) =45% as determined by echocardiography or multi-channel radionuclide angiography (MUGA); 9) Adequate bone marrow reserve without blood transfusion is defined as: ? Absolute lymphocyte count (ALC) =300 /mm3; ? Platelet =10.000 /mm3; ? Hemoglobin > 5.0g/ dL; 10) Non-mobilized monopheresis or peripheral blood collection cells must be available for CAR T cell production; 11) Patients using the following drugs should meet the following conditions: ? Steroids: The therapeutic dose of steroids must be discontinued 72 hours prior to infusion of CD19+CXCR5. Physiological replacement doses of steroids, however, are permitted; ? Immunosuppression: Any immunosuppressive drug must be discontinued =4 weeks prior to inclusion; ? Anti-proliferative therapy in addition to lymphatic depletion chemotherapy within 2 weeks of infusion; ? CD20 antibody related therapy must be discontinued within 4 weeks or 5 half-lives (whichever is longer) prior to infusion; ? CNS prophylaxis must be discontinued 1 week prior to infusion of CD19+CXCR5 (e.g., intrathecal methotrexate). 12) Women of reproductive age and all male subjects must agree to use highly effective contraceptive methods until at least 12 months after CD19+CXCR5 infusion and until 2 consecutive PCR tests show no CAR T cells in the body.
Exclusion criteria
Exclusion criteria: 1) Patients previously treated with any gene therapy product, including CAR-T; 2) Patients with detectable cerebrospinal fluid malignant cells or brain metastases, or a history of primary CNS lymphoma; 3) Patients with testicular invasion, including those who have had testicular removal; 4) Patients who currently have or have a history of central nervous system diseases, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases or any autoimmune diseases associated with central nervous system; 5) Patients who received chemotherapy other than lymphocyte clearance chemotherapy within 2 weeks prior to CD19+CXCR5 infusion; 6) Screening patients who received other study medications within the previous 30 days; 7) Patients who received radiotherapy within 2 weeks prior to infusion; 8) Patients with active hepatitis B (defined as HEPATITIS B VIRUS DNA test value > 500 IU/mL) or hepatitis C (HCV RNA positive); 9) HIV positive or treponema pallidum positive patients; 10) patients with uncontrolled acute life-threatening bacterial, viral or fungal infection (e.g. positive blood culture =72 hours prior to infusion); 11) Screening patients with unstable angina and/or myocardial infarction within the previous 6 months; 12) Patients with prior or concurrent malignancy, except for: ? Basal or squamous cell carcinoma that has been adequately treated (adequate wound healing is required prior to enrollment); ? Carcinoma in situ of cervical or breast cancer that has been treated curatively and has shown no signs of recurrence for at least 3 years prior to the study; ? The primary malignancy has been completely resected and in complete remission for =5 years. 13) Pregnant or lactating women; 14) Patients with arrhythmia without medical management control; 15) Patients receiving oral anticoagulant therapy within 1 week prior to CAR T cell infusion; 16) Patients who have previously received any adoptive T cell therapy; 17) have active neuroautoimmune or inflammatory disorders (e.g. Guillian-Barre syndrome, AMyotrophic lateral sclerosis); 18) Other conditions that the investigator considers should not be included in this clinical trial, such as poor compliance, etc.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall response rate; | — |
Countries
China
Contacts
Public ContactGuowei Li
Outcome results
None listed