This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.

This is a single-centre, randomised, open label Phase I clinical trial of CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma. Following informed consent and registration to the trial, Patients will receive the allogeneic CD19 CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.

Inclusion Criteria:

Enrollment for enough male or female patients with CD19+ hematological malignancies, without regimens for cure (autologous or allogeneic stem cell transplantation), and having a poor prognosis (several months to 2 years) under current optional regimens

1. Age ranges from 18 to 70 years old

2. Expected survival time longer than 12 weeks

3. Performance status score 0-2

4. Pathologically confirmed CD19+ lymphoma (CD19+ follicular lymphoma, Mantle cell lymphoma, diffuse large B cell lymphoma) and meets at least one of follows:

   1. having received at least 2-4 cycles of combined chemotherapy (excluding monoclonal antibody monotherapy, such as rituximab) but do not reach a complete response; recurrent disease; not applicable for conventional stem cell transplantation; being partial responsible or stable but not complete responsible after the latest therapy
   2. recurrence develops after stem cell transplantation
   3. diagnosis confirmed but refusing to receive conventional therapy

5. Creatinine<2.5 mg/dl；

6. alanine aminotransferase/aspartate aminotransferase lower than 3 folds of normal range

7. Bilirubin<2.0 mg/dl；

8. Venous channel available and no contraindications for leukocyte collection

9. Reliable contraception from the beginning to 30 days after discontinuation of therapy

10. Informed consent signed

Exclusion Criteria:

1. Central nerve system invasion with symptoms
2. Other concurrent uncontrolled malignancies
3. Hepatitis B infection or active period of hepatitis C, HIV infection
4. Other uncontrolled diseases hampering the intervention in the study
5. Coronary heart disease, angina, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious cardiovascular or cerebrovascular diseases.
6. Grade 2-3 or uncontrolled hypertension
7. History of uncontrolled mental disease
8. Not suitable for participation judged by researchers
9. Immunosuppressive agents administered due to organ transplantation, not including recent or current inhaled corticosteroid
10. Medical history of mental diseases or abnormities of lab tests might increase the risks of participation in study or drug administration, or interfering the results
11. Screening suggesting transfection efficiency of targeting cells lower than 30% or cell expansion deficiency under CD3/CD28 (cluster of differentiation 3,CD3)stimulation (less than 5 folds)
12. Unstable pulmonary embolism, deep venous thromboembolism or other major arterial/venous thromboembolism events develop in 30 days before the randomization. If anti-coagulation therapy is received, the treatment dose should reach stability before the randomization.
13. Pregnancy or lactation, or pregnancy planned during the study or in 2 months after the study
14. Reliable contraception not accepted during the study or in 2 months after the study. Female subjects are required to provide negative results from serum or urine pregnancy test 48 hours before therapy
15. Systematic active or uncontrolled infection (excluding infection of urinary tract or upper respiratory tract infection) in 14 days before the randomization
16. Informed consent not signed or study rules violated