B-cell Non-Hodgkin's Lymphoma
Conditions
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALCD19/CD20 Dual-CAR-T cells
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.
Sponsors
China Immunotech Pharmaceuticals Co.Ltd.
Beijing Tsinghua Chang Gung Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of adverse events | 6months | Percentage of participants with adverse events. |
| Objective remission rate(ORR) | 6 months | The percentage of participants who achieved complete remission (CR) and partial remission over all participants. |
Secondary
| Measure | Time frame |
|---|---|
| Overall-Survival(OS) | 6 months |
| Relapse-Free Survival(RFS ) | 6 months |
Other
| Measure | Time frame |
|---|---|
| Persistence of CAR-T cells in vivo | 6 months |
Countries
China
Outcome results
None listed