CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);
2. Relapsed or refractory B cell hematological malignancies (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;
   5. Relapse after hematopoietic stem cell transplantation;
   6. Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;
3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
6. Estimated survival time ≥ 12 weeks;
7. ECOG performance status 0 to 2;
8. Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion.
9. Patients 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 urinary tract infection and bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
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, or bilirubin \>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 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 · 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)；Multiple myeloma (MM), Overall response rate (ORR)；MM, Overall survival (OS)；Quality of life

• Administration of CD19/BCMA Targeted CAR T-cells and dasatinib · EXPERIMENTAL · Dose levels of CAR-T cells are based on clinical trials of similar foreign products. Meanwhile, dasatinib would be combined as the following regimens: 1) Dasatinib preconditioning CAR-T cells during the manufacturing; 2) Dasatinib for the intervention of cytokine release storm after CAR-T cell infusion; 3) Dasatinib for the intervention of neurotoxicities after CAR-T cell infusion; 4) Dasatinib for the phase of CAR-T cell decreasing.
• Administration of CD19/BCMA Targeted CAR T-cells · EXPERIMENTAL · Dose levels of CAR-T cells are based on clinical trials of similar foreign products.

A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.