CD19 CAR-T Cells With CRS Suppression Technology for r/r CD19+ Acute Lymphoblastic Leukemia

Chimeric Antigen Receptor T Cells Against CD19 With Cytokine Release Syndrome (CRS) Suppression Technology for Refractory/Relapsed CD19+ Acute Lymphoblastic Leukemia

This is a single center,randomized ,two-cohorts, open-label ,phase 1/2 study to evaluate the efficacy and safety of T cells expressing CD19 chimeric antigen receptors treatment for relapsed/refractory CD19+ acute lymphoblastic leukemia patients.

Relapsed/refractory CD19 + acute lymphoblastic leukemia patients were randomly enrolled in this study to compare the efficacy and safety between two cohorts: 1. CD19 CAR-T cells； 2. CD19 CAR-T cells with CRS suppression technology.

Inclusion Criteria:

1. Age 6 to 65
2. Voluntary informed consent is given
3. Expected survival ≥12 weeks
4. Relapsed or refractory CD19+ acute leukemia, ineligible for allo-HSCT,or relapse after auto-HSCT
5. Organ function: (1)Left ventricular ejection fractions≥ 0.6 by echocardiography (2)ALT ≤3 times of ULN, or bilirubin <2.0 mg/dl (3)Creatinine < 2 mg/dl and less than 2.5 × normal for age (4)Prothrombin time and activated partial thromboplastin time < 2 times of ULN (5)Arterial oxygen saturation> 92%
6. Karnofsky score ≥ 60 ;
7. No history of combined chemotherapy in the recent 1 month and no immunotherapy in the recent 3 months;

Exclusion Criteria:

1. Uncontrolled active infections
2. Active hepatitis B or hepatitis C infection
3. HIV infection
4. History of myocardio infarction in the past 6 months, or history of severe arrhythmia
5. Congenital immunodeficiency
6. Pregnant or lactating women
7. History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
8. Previous treatment with any gene therapy products