Clinical Trial Using CAR- T Cells for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies

Inclusion Criteria: 1. Subjects must have relapsed or refractory ALL, lymphoma or CLL treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs). Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti-CD20 monoclonal antibody. Subjects with transformed FL, MZL, or CLL/SLL must have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL. Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant. 2. 2\. The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available. 3. Age 2 to 70 years. 4. Performance status: Adult Subjects: ECOG ≤ 2 for patients ≥ 16 years; Subjects \< 16 years of age: lansky ≥ 50% 5. Normal Organ and Marrow Functioning (supportive treatment is allowed according to institutional standards, i.e. filgrastim, transfusion) • Total Bilirubin ≤ 2; AST (SGOT) ≤ 5 times the upper limit of normal; ALT (SGTP) ≤ 5 times the upper limit of normal; Serum creatinine ≤ 1.5; Pulse oximetry \>91% on room air; No dyspnea or mild dyspnea (≤ Grade 1); Forced expiratory volume in 1 s (FEV1) ≥50% or carbon monoxide diffusion test (DLCO) ≥50% of predicted level; Left ventricular ejection fraction ≥ 45% confirmed by echocardiogram; Subjects must have the following hematologic function parameters: Neutrophils \> 1000/uL; Absolute Lymphocyte Count \> 100/uL; Platelets ≥ 50,000/L Patient should not be excluded if change of the above parameters due to spinal cord disease infiltration; 6. Prior therapy wash-out - At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives, Blinatumomab with 4 months prior CAR-T infusion. 7. For women of reproductive potential: use a highly effective contraceptive for at least 1 month prior to screening and agree to use a method during study participation and for an additional 4 months after CAR T-cell administration has ended. 8. Subjects must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. Autologous transplant within 6 weeks of planned CAR-T cell infusion; 2. History of allogeneic stem cell transplant 4 months prior CAR T cell infusion. 3. Use of immunosuppression therapy; • Patients must have completed immunosuppression therapy; Systemic corticosteroid therapy must be stopped more than 72 hours after infusion; Systemic drugs for graft-versus-host disease should be withheld at least 4 weeks prior to infusion; 4. Presence of graft-versus-host disease Grade ≥ 2; 5. Receiving CAR T cell treatment outside of this protocol; 6. Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration. 7. History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast). 8. HIV infection; HTLV 9. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements. 10. Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. 11. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy 12. Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) 13. Serious and/or potentially fatal medical conditions 14. Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease. 15. History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months. 16. Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage therapies for treatment related toxicities;