CD19/CD20 Dual-CAR-T in B-cell Non-Hodgkin's Lymphoma Patients.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CD19/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 for at least 2 days before infusion. |
Biological: CD19/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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Relapse-Free Survival(RFS ) [6 months]
- Overall-Survival(OS) [6 months]
Other Outcome Measures
- Persistence of CAR-T cells in vivo [6 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years
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NHL confirmed by cytology or histology, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, etc.
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Relapse or refractory after at least second-line treatment;
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With evaluable target lesions.Measurable target lesions: lymph nodes>1.5x1.0cm, extranodal lesions>1.0x1.0cm;
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Double positive expression of CD19 / CD20 in B cells;
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ECOG score 0-2 points;
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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%.
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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;
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Patients who voluntarily sign informed consent and are willing to comply with treatment plans.
Exclusion Criteria:
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Active infections that are difficult to control;
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Active hepatitis B, active hepatitis C, human immunodeficiency virus (HIV) antibody positive, and Treponema pallidum antibody test positive;
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The tumor invades the central nervous system or primary CNS lymphoma;
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Anti-GVHD (acute or chronic) treatment is being performed within 4 weeks before apheresis and cell infusion;
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Have undergone the following treatments:
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Those who have received chemotherapy or radiotherapy 5 days before apheresis;
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Those who have used drugs that stimulate the production of bone marrow hematopoietic cells within 5 days before apheresis;
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Received donor lymphocyte infusion (DLI) within 6 weeks before cell infusion;
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Have received autologous hematopoietic stem cell transplantation (HSCT) 3 months before apheresis, or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 12 months;
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Have used any gene therapy products before;
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History of epilepsy or other central nervous system diseases; or clinically diagnosed as having severe thyroid dysfunction; or active autoimmune diseases;
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History of other malignant tumors that have not been remission for at least 3 years ;
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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;
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Pregnant or lactating women;
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The investigator believes that there are other factors that are not suitable for selection or that affect subjects' participation or completion of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tsinghua Changgung Hospital | Beijing | Beijing | China |
Sponsors and Collaborators
- Beijing Tsinghua Chang Gung Hospital
- China Immunotech Pharmaceuticals Co.Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HXYT-012