CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* 1\. Gender unlimited，18\< Age;
* 2\. Patients diagnosed with B-cell acute lymphoblastic leukemia through histological or immunophenotyping tests; The clear diagnosis of B-cell non Hodgkin's lymphoma by cellular or histopathological examination mainly includes diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma
* 3\. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

  1. CR not achieved after standardized chemotherapy;
  2. CR achieved following the first induction, but CR duration is less than 12 months;
  3. Ineffectively after first or multiple remedial treatments;
  4. 2 or more relapses;
* 4\. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \>5% (by morphology), and/or \>1% (by flow cytometry);
* 5\. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
* 6\. Relapsed or refractory B-NHL (meeting one of the following conditions):

  1. No response or relapse after second-line or above chemotherapy regimens;
  2. Primary drug resistance;
  3. Relapse after auto-HSCT;
* 7\. At least one assessable tumor lesion per Lugano 2014 criteria;
* 8\. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
* 9\. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
* 10\. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
* 11\. Estimated survival time ≥ 3 months;
* 12\. ECOG performance status 0 to 2;
* 13\. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

* 1\. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
* 2\. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
* 3\. Pregnant/lactating women, or male or female patients with fertility who are unwilling to take effective contraceptive measures during the study period or at least 6 months after the last cell infusion
* 4\. Patients with HIV infection;
* 5\. Active infection of hepatitis B virus or hepatitis C virus;
* 6\. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
* 7\. Other uncontrolled diseases that were not suitable for this trial;
* 8\. Individuals who have received CAR-T therapy, CAR-NK therapy, or any other gene modified cell therapy product within 6 months;
* 9\. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

主要终点：Dose-limiting toxicity (DLT) · Adverse events assessed according to NCI-CTCAE v5.0 criteria · Up to 28 years after Treatment；Incidence of treatment-emergent adverse events (TEAEs) · Incidence of treatment-emergent adverse events \[Safety and Tolerability\] · Up to 2 years after Treatment
次要终点：Overall response rate ,ORR；Duration of remission ,DOR；Event-free survival, EFS；Overall survival, OS

• Administration of CD19-BAFF Targeted CAR T-cells · EXPERIMENTAL · Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.

Clinical Trial for the safety and efficacy of CD19-BAFF CAR-T cells therapy for refractory/relapsed B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.