CD19 CART Cells for Patients With Relapse and Refractory CD19+ B-cell Lymphoma.

Study Overview
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Brief Summary
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This is a clinical study to observe the maximum tolerated dose (MTD) and the safety and feasibility of chimeric antigen receptor 19 (CD19 CART) 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. Maximum tolerated dose climbing test is expected into the group of 9 cases of patients. And Phase II expected into the group of 11 subjects, selected the above safe dose, carrying out a research into the clinical effectiveness. Subjects will be collected their T cells and modify them, the modification is a genetic change, that CD19:4-1BB:CD28: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 observe the MTD and to assess the safety and feasibility of CART cells in the patients with relapsed and refractory CD19+ B cell lymphoma.

Official Title
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Phase I/II Study of CD19 CART Cells for Patients With Relapse and Refractory CD19+ B-cell Lymphoma.

Conditions
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B Cell Lymphoma

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide
* Biological: CD19 CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 18 years to 70 years, expected survival > 3 months; 2. CD19 positive B-cell lymphoma; 3. KPS >80; 4. Having at least one measurable lesions; 5. 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）; 6. No serious allergic constitution; 7. No other serous diseases that conflicts with the clinical program; 8. No other cancer history; 9. No serious mental disorder; 10. Informed consent is signed by a subject or his lineal relation. Exclusion Criteria: 1. Pregnant or lactating women; (female participants of reproductive potential must have a negative serum or urine pregnancy test); 2. Uncontrolled active infection, HIV infection, syphilis serology reaction positive; 3. Active hepatitis B or hepatitis C infection; 4. Recent or current use of glucocorticoid or other immunosuppressor; 5. With severe cardiac, liver, renal insufficiency, diabetes and other diseases; 6. Transaminase >2.5ULN, Bilirubin >3ULN，Creatinine>1.25ULN 7. Participate in other clinical research in the past three months; previously treatment with any gene therapy products; 8. 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: CD19 CART<br>patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of CD19 CART cells. The CD19 CART cells are to be administered on day0,day1,day2. | Drug: Fludarabine<br>* Fludarabine 30 mg/m2/day IV for 3 days.<br>Drug: Cyclophosphamide<br>* patients will receive a standard pre-conditioning regime with cyclophosphamide 0.8g/m2/day IV for 2 days.<br>Biological: CD19 CART<br>* CD19 CART 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 | 
| observe the maximum tolerated dose (MTD) |  | 2 months | 
| objective response rate | CR+PR | 2 years | 
| disease control rate | CR+PR+SD | 2 years | 
| overall survival | OS | 2 years | 
| Progression-Free Survival |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine duration of in vivo survival of CD19 CART cells | CD19 CART vector sequences will be performed by Q-PCR | 2 years | 
| Peripheral blood cytokines | IL-6、IL-10、IFN-γ、TNF-α | 2 months | 
| subgroup of T cell | CD3、CD4、CD8 | 2 years |