This is a single-arm, open-label pilot study to evaluate the safety and efficacy of CD19-targeted allogenic CAR-T cells (19UCART) in patients with relapsed/refractory B-cell hematologic malignancies. 12 patients are planned to be enrolled in the dose-escalation trial. The primary objective of the study is to evaluation of the safety and feasibility of 19UCART for the treatment of relapsed/refractory B-cell hematologic malignancies. The secondary objective is to evaluate the efficacy of 19UCART for the treatment of relapsed/refractory B-cell hematologic malignancies. The exploratory objective is to evaluate expansion, persistence and ability of 19UCART to deplete CD19 positive cells in patients with relapsed/refractory B-cell hematologic malignancies.

Inclusion Criteria:

1. Voluntary participation in this trial with signed informed consent.
2. Diagnosis of B-cell hematologic malignancy according to the 2017 WHO classification, including B-acute lymphoblastic leukemia (B-ALL) and mature B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), mantle-cell lymphoma (MCL), etc.
3. Refractory or relapsed B-cell malignancy defined as failure to achieve complete remission after standard therapy, or relapse after achieving remission with first-line or salvage therapy.
4. Persistence of minimal residual disease (MRD) positivity despite hematologic remission in B-cell acute lymphoblastic leukemia (ALL).
5. At least one measurable lesion ≥1.5 cm in longest diameter by IWG revised criteria for relapsed/refractory lymphoma.
6. Age 18-70 years; both sexes eligible.
7. Expected survival ≥12 weeks.
8. Adequate organ function as follows (no blood products or growth factors within 14 days before first infusion):

1). Hematology: A. White blood cell count (WBC) ≥3.0×10⁹/L B. Absolute neutrophil count (ANC) ≥1.5×10⁹/L C. Platelet count (PLT) ≥100×10⁹/L D. Hemoglobin (Hb) ≥90 g/L 2). Renal: A. Serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min 3). Cardiac: A. Left ventricular ejection fraction (LVEF) ≥50 % B. QTc (Fridericia) ≤450 ms (men) or ≤470 ms (women) 4). Hepatic: A. Total bilirubin ≤1.5×ULN B. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver involvement) 5). Coagulation: A. International normalized ratio (INR) or Prothrombin time (PT) ≤1.5×ULN B. Activated partial thromboplastin time (APTT) ≤1.5×ULN 6). Pulmonary: Diffusing capacity of the lung (DLCO) ≥50 % of predicted (with or without correction for anemia/alveolar volume).

9. ECOG performance status 0-2 at screening. 10. LVEF ≥50 % and no pericardial effusion. 11. At least 2 weeks since last prior therapy (radiation, chemotherapy, monoclonal antibody, or other systemic treatment).

12. Recovery to ≤CTCAE Grade 1 for any preceding serious adverse event (SAE). 13. WOCBP* not surgically sterilized must use highly effective contraception from study start through 6 months after last dose; men with WOCBP partners must use highly effective contraception through 3 months after last dose. WOCBP must have negative serum β-hCG within 7 days before first dose and must not be breastfeeding.

14. Ability to comply with study visit schedule and all protocol requirements.

*WOCBP = women of child-bearing potential

Exclusion Criteria:

• Subjects with any of the following conditions are ineligible for this trial:

  1. Known hypersensitivity, allergic reaction, intolerance, or contraindication to 19UCART or any study-drug component (including fludarabine, cyclophosphamide, or tocilizumab), or history of severe anaphylaxis.

  2. Post-allo-HSCT relapse with active graft-versus-host disease requiring systemic corticosteroids or other immunosuppressants.

  3. Uncontrolled active infection of any etiology.

  4. Active hepatitis B, hepatitis C, or tuberculosis.

  5. HIV or syphilis infection.

  6. Active autoimmune disease or history of severe autoimmune disorder (as judged by the PI) requiring prolonged immunosuppressive therapy.

  7. Congenital or acquired immunodeficiency syndromes.

  8. New York Heart Association (NYHA) class III or IV heart failure, unstable angina, myocardial infarction within 6 months, or sustained (>30 s) ventricular arrhythmia.

  9. History of epilepsy or other significant central nervous system disorders.

  10. Extra-nodal lymphomatous involvement of brain, lung, or gastrointestinal tract.

  11. Prior malignancy other than:

      1. Curatively resected non-melanoma skin cancer (e.g., basal-cell carcinoma)
      2. Curatively treated carcinoma in situ (cervical, bladder, breast, etc.)

  12. Systemic high-dose corticosteroids within 2 weeks before study entry.

  13. Pregnancy, lactation, or intention to become pregnant within 6 months.

  14. Participation in another clinical trial within 1 month.

  15. Anticipated need for any other systemic anti-neoplastic therapy during the study.

  16. Major surgery within 14 days before first study-drug administration.

  17. Any condition that, in the investigator's opinion, could increase patient risk or interfere with study results.