Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical Research

Inclusion Criteria: 1. The patient or his/her guardian voluntarily signed the informed consent. 2. Meeting one of the following conditions: 1. Patients with relapsed or refractory B-cell lymphoma who have received CD20 antibodies (such as rituximab) and at least two chemotherapy treatments, one of which should include anthracyclines. After these regimens, patients maintained SD (SD duration ≤12 months) or disease progression. 2. Partial remission (PR) or minimal residual lesions after two chemotherapy treatments. 3. Recurrence after autologous hematopoietic stem cell transplantation. 4. Extramedullary recurrence or residual leukemia cells ≥ 0.01% in bone marrow after allogeneic hematopoietic stem cell transplantation. 5. Patients with relapsed or refractory B-ALL who not suitable for hematopoietic stem cell transplantation. 3. CD19 expression was positive by immunohistochemistry or flow cytometry (\>30%)，accept the results of this peripheral blood mononuclear cells or previous report from a Class A tertiary hospital before peripheral blood collection. 4. At least one measurable lesion at baseline, according to the initial assessment, staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition). 5. Expected survival time greater than 12 weeks. 6. The baseline ECOG score was 0 or 1. 7. Patients with proper organ function: 1. Kidney function is defined as: Serum creatinine ≤1.5 times ULN, or; The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/ min/1.73m2. 2. Liver function is defined as: ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included. 3. Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment. 8. Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45. 9. Patients using the following drugs must meet the following conditions: 1. Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, hydrocortisone or its equivalent \< 6- 12mg/mm2/ day. 2. Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks before the informed consent is signed. 3. Anti-proliferative therapy in addition to preconditioning chemotherapy 2 weeks prior to Meta10- 19 infusion. 4. Treatment for CNS disease must be stopped 1 week before Meta10-19 infusion (e.g., intrathecal methotrexate) 10. The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or less, such as hair loss, which the researchers have determined is not recoverable in a short period of time) is suitable for pretreatment chemotherapy and CAR-T cell therapy. 11. Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR-T cells in vivo. Exclusion Criteria: 1. Patients with present or history of central nervous system diseases such as seizures disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. 2. Patients who had received chemotherapy other than preconditioning chemotherapy within 2 weeks prior to Meta10-19 infusion. 3. Patients who participated in other clinical trials within 30 days prior to enrollment. 4. Patients with active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, concomitant hepatitis B virus DNA level \>1000 copies/ml) or hepatitis C (HCV RNA positive). 5. Patients with HIV antibody positive or treponema pallidum antibody positive. 6. Patients with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g. positive blood cultures ≤72 hours before Meta10-19 infusion). 7. Patients with unstable angina pectoris and/or myocardial infarction within 6 months prior to enrollment. 8. Patients with history of other malignancies, but the following conditions can be enrollment: 1. Adequately treated basal or squamous cell carcinoma (requiring adequate wound healing before signing informed consent). 2. Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated therapeutically, has shown no signs of recurrence for at least 3 years prior to the signing of the informed consent. 3. The primary malignancy has been completely resected and in complete remission for ≥5 years. 9. Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age are positive). 10. Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis). 11. Other conditions that the investigator considered should not be enrolled in this clinical study. 12. B-ALL patients meeting one of the following conditions: 1. Isolated extramedullary recurrence. 2. Central nervous system leukemia was treated within 1 week prior to CAR T cell infusion.