cd19/cd20 dual-car-t in b-cell non-hodgkin's lymphoma patients.

Conditions: B-cell Non-Hodgkin's Lymphoma

Summary: this is a single center, single arm, open-label, phase i study to evaluate the safety and efficacy of cd19/cd20 dual-car-t cells in patients with refractory or relapsed b-nhl.

this phase i study is designed as a pilot trial evaluating the safety and efficacy of cd19/cd20 dual-car-t cell therapy in subjects with refractory and relapsed b-nhl. subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of cd19/cd20 dual-car-t cells. safety and efficacy of cd19/cd20 dual-car-t cells therapy will be monitored. the purpose of current study is to determine the clinical efficacy and safety of cd19/cd20 dual-car-t cells therapy in patients with refractory and relapsed b-nhl.

Eligibility criteria:
inclusion criteria: 1. age ≥18 years 2. nhl confirmed by cytology or histology, including diffuse large b-cell lymphoma, follicular lymphoma, mantle cell lymphoma, etc. 3. relapse or refractory after at least second-line treatment; 4. with evaluable target lesions.measurable target lesions: lymph nodes\>1.5x1.0cm, extranodal lesions\>1.0x1.0cm; 5. double positive expression of cd19 / cd20 in b cells; 6. ecog score 0-2 points; 7. good organ function: blood routine: absolute neutrophil count (anc) ≥1.0×109/l; hemoglobin (hb) ≥80 g/l; platelet count (plt) ≥50×109/l; blood biochemistry: total bilirubin≤3×upper limit of normal (uln), aspartate aminotransferase (ast) and alanine aminotransferase (alt)≤3×upper limit of normal (uln); pulmonary function: ≤ctcae grade 1 dyspnea and sao2≥92% in indoor air environment; heart function: left ventricular ejection fraction (lvef) ≥50%. 8. women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside; 9. patients who voluntarily sign informed consent and are willing to comply with treatment plans. exclusion criteria: 1. active infections that are difficult to control; 2. active hepatitis b, active hepatitis c, human immunodeficiency virus (hiv) antibody positive, and treponema pallidum antibody test positive; 3. the tumor invades the central nervous system or primary cns lymphoma; 4. anti-gvhd (acute or chronic) treatment is being performed within 4 weeks before apheresis and cell infusion; 5. have undergone the following treatments: * those who have received chemotherapy or radiotherapy 5 days before apheresis; * those who have used drugs that stimulate the production of bone marrow hematopoietic cells within 5 days before apheresis; * received donor lymphocyte infusion (dli) within 6 weeks before cell infusion; * have received autologous hematopoietic stem cell transplantation (hsct) 3 months before apheresis, or received allogeneic hematopoietic stem cell transplantation (allo-hsct) within 12 months; * have used any gene therapy products before; 6. history of epilepsy or other central nervous system diseases; or clinically diagnosed as having severe thyroid dysfunction; or active autoimmune diseases; 7. history of other malignant tumors that have not been remission for at least 3 years ; 8. any of the following cardiovascular diseases occurred within 6 months of the screening period, including nyha heart function grade iii or iv heart failure, cardiovascular angioplasty or stent, myocardial infarction, unstable angina, or other clinical symptoms significant heart disease; 9. pregnant or lactating women; 10. the investigator believes that there are other factors that are not suitable for selection or that affect subjects' participation or completion of the study.