The Safety and Efficacy of CART-19 Cells in Relapse and Refractory Patients With CD19+ B-cell Lymphoma

Study Overview
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Brief Summary
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This is a clinical study to observe the safety and feasibility of chimeric antigen receptor 19 (CART-19) cells in relapsed and refractory patients with CD19+ B cell lymphoma.

Detailed Description
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This is a study for the patients with B cell lymphoma. Subjects will be staged and the suitability of their T cells for CART-19 manufacturing will be determined at entry phase. Subjects will be collected their T cells and modify them, the modification is a genetic change, that CD19:4-1BB:CD3 modified T cells, in order to tells the T cells to recognize their target tumor cells and potentially kill them, but not other normal cells in the subject's body. The CART cells will then be expanded in vitro and then administered to subjects. The purpose of this study is to assess ssess the safety and feasibility of CART-19 cells in the patients with relapsed and refractory CD19+ B cell lymphoma.

Official Title
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The Safety and Efficacy of CART-19 Cells in Relapse and Refractory Patients With CD19+ B-cell Lymphoma

Conditions
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B Cell Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Fludarabine
* Biological: CART-19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years to 70 years, expected survival > 3 months; CD19 positive B-cell lymphoma; KPS >80; Having at least one measurable lesions; Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; bone marrow: WBC ≥ 3.0×109/L, Hb ≥90 g/L, PLT ≥ 80×109/L）; No serious allergic constitution; No other serous diseases that conflicts with the clinical program; No other cancer history; No serious mental disorder; Informed consent is signed by a subject or his lineal relation. Exclusion Criteria: Pregnant or lactating women; (female participants of reproductive potential must have a negative serum or urine pregnancy test); Uncontrolled active infection, HIV infection, syphilis serology reaction positive; Active hepatitis B or hepatitis C infection; Recent or current use of glucocorticoid or other immunosuppressor; With severe cardiac, liver, renal insufficiency, diabetes and other diseases; Transaminase >2.5ULN, Bilirubin >3ULN，Creatinine>1.25ULN Participate in other clinical research in the past three months; previously treatment with any gene therapy products; Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: CART-19<br>patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of CART-19 cells. The CART-19 cells are to be administered on day0,day1,day2. | Drug: Cyclophosphamide<br>* patients will receive a standard pre-conditioning regime with cyclophosphamide 0.8-1.0g/m2/day IV for 2 days(Day-5 to day-4).<br>Drug: Fludarabine<br>* Fludarabine 25 mg/m2/day IV for 3 days (Day-5 to day-3).<br>Biological: CART-19<br>* CART-19 cells will be administered using a split dose on day0(10%), 1(30%), and 2(60%) after completion of the chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety as assessed by the occurence of study related adverse events | monitor the occurence of study related adverse events | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy assessed by anti-tumor activity of CART-19 cells | anti-tumor activity of CART-19 cells will be determined in a follow-on study | 2 years | 
| duration of CART-19 | Determine duration of in vivo survival of CART-19 cells | 2 years |