CD19/CD20 Dual-CAR-T in B-cell Non-Hodgkin's Lymphoma Patients.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Study of CD19/CD20 Dual CAR-T Cells in the Treatment of Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma(B-NHL)

Conditions
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B-cell Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Biological: CD19/CD20 Dual-CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years NHL confirmed by cytology or histology, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, etc. Relapse or refractory after at least second-line treatment; With evaluable target lesions.Measurable target lesions: lymph nodes>1.5x1.0cm, extranodal lesions>1.0x1.0cm; Double positive expression of CD19 / CD20 in B cells; ECOG score 0-2 points; 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%. 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; Patients who voluntarily sign informed consent and are willing to comply with treatment plans. Exclusion Criteria: Active infections that are difficult to control; Active hepatitis B, active hepatitis C, human immunodeficiency virus (HIV) antibody positive, and Treponema pallidum antibody test positive; The tumor invades the central nervous system or primary CNS lymphoma; Anti-GVHD (acute or chronic) treatment is being performed within 4 weeks before apheresis and cell infusion; 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; History of epilepsy or other central nervous system diseases; or clinically diagnosed as having severe thyroid dysfunction; or active autoimmune diseases; History of other malignant tumors that have not been remission for at least 3 years ; 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; Pregnant or lactating women; The investigator believes that there are other factors that are not suitable for selection or that affect subjects' participation or completion of the study.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19/CD20 Dual-CAR-T cells<br>CD19/CD20 Dual-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest for at least 2 days before infusion. | Biological: CD19/CD20 Dual-CAR-T cells<br>* CD19/CD20 Dual-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest at least for 2 days before infusion. CD19/CD20 Dual-CAR-T cells will be intravenously infused with a escalated dose of 2E6、6E6、1E7、3E7 cells/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of adverse events | Percentage of participants with adverse events. | 6months | 
| Objective remission rate(ORR) | The percentage of participants who achieved complete remission (CR) and partial remission over all participants. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-Free Survival(RFS ) |  | 6 months | 
| Overall-Survival(OS) |  | 6 months |