CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Inclusion criteria only for B-ALL:

  1. Male or female aged 3-70 years;
  2. Histologically confirmed diagnosis of B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
  3. Relapsed or refractory CD19+ B-ALL (meeting one of the followingconditions):

     1. CR not achieved after standardized chemotherapy;
     2. CR achieved following the first induction, but CR duration isless 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 flowcytometry);
  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;
* Inclusion criteria only for B-NHL:

  1. Male or female aged 18-75 years;
  2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHOClassification Criteria for Lymphoma (2016);
  3. Relapsed or refractory B-NHL (meeting one of the followingconditions):

     1. No response or relapse after second-line or abovechemotherapy regimens;
     2. Primary drug resistance;
     3. Relapse after auto-HSCT;
  4. At least one assessable tumor lesion per Lugano 2014 criteria;
* Common inclusion criteria for B-ALL and B-NHL:

  1. Highly suspected or confirmed central nervous system involvement of hematological malignancies;
  2. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
  3. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
  4. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
  5. Estimated survival time ≥ 3 months;
  6. ECOG performance status 0 to 2;
  7. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

Subjects with any of the following exclusion criteria were not eligible for this trial:

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 (or lactating) women;
4. Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
7. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
8. Creatinine\>2.5mg/dl, or ALT / AST \> 3 times of normal amounts,orbilirubin\>2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk ofpatients 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 · Baseline up to 28 days after CAR T-cells infusion；Incidence of treatment-emergent adverse events (TEAEs) · Incidence of treatment-emergent adverse events \[Safety and Tolerability\] · Up to 2 years after CAR T-cells infusion
次要终点：B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)；B-ALL, Overall survival (OS)；B-ALL, Event-free survival (EFS)；B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)；B-NHL, disease control rate (DCR)；Quality of life；IADL score；ADL score

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

A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies