The Safety and Efficacy of CART-19 Cells in B-cell Acute Lymphoblastic Leukemia (B-ALL).

The Safety and Efficacy of CART-19 Cells in Relapse and Refractory Patients With CD19+ B-cell Acute Lymphoblastic Leukemia.

This is a study for patients who have been previously treated for B-ALL. The purpose of this study is to determine the safety and feasibility of CART-19 cells to the patients with relapsed and refractory CD19+ B-ALL.

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 large numbers of peripheral blood mononuclear cells (PBMC) for CART-19 manufacturing. The T cells will be purified from the PBMC, transduced with CART-19 lentiviral vector, expanded in vitro and then administered to subjects.

Subjects will have blood tests to assess safety and efficacy, and persistence of the CART-19 cells at regular intervals through four weeks after their last infusion of the study. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly for two years with a physical examination, blood tests, bone marrow aspirate, minimal residual disease (MRD) and persistence of CART-19. Following this evaluation, subjects will be evaluated health problems every year for an additional thirteen years.

Inclusion Criteria:

1. 4 years to 70 years, expected survival > 3 months
2. CD19 positive B-cell acute lymphoblastic leukemia
3. Karnofsky Performance Status (KPS) >70
4. Relapsed after allogeneic or autologous stem cell transplantation (SCT);
5. Cardiac function: 1-2 levels; Liver: TBIL≤3 Upper Limit of Normal (ULN)，aspartate aminotransferase (AST) ≤2.5 ULN，ALT ≤2.5 ULN; kidney: Cr≤1.25 ULN; bone marrow: White Blood Cell (WBC) ≥ 3.0×109/L, Hb ≥90 g/L, Platelet (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 >2.5 ULN, Bilirubin >3 ULN，Creatinine>1.25 ULN
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