Plan adjustment

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.

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.