This study aims to evaluate the safety and efficacy of humanized Anti-CD19 Chimeric Antigen Receptor-T cell (CAR19T2 T cell) in children with refractory/relapsed B-cell acute lymphoblastic leukemia/lymphoma.
CD19 CAR-T cells treating B-cell hematological malignancies have achieved unprecedented success. In this study, we investigated new third-generation autologous T cells (CAR19T2 T cells) genetically modified with humanized anti-CD19 construct incorporating CD28 and Toll-like receptor 2 (TLR2) costimulatory domains. CAR19T2 T cells will be modified before the infusion to those which could identify and kill the tumor cells (CD19+ cells). This study aims to evaluate the safety and efficacy of humanized Anti-CD19 Chimeric Antigen Receptor T cell (CAR19T2 T Cell) in children with refractory/relapsed B-cell acute lymphoblastic leukemia/lymphoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Drug: Fludarabine, Administered intravenously Drug: Cyclophosphamide, Administered intravenously
Guangdong Zhaotai Cell Bio-tech Co., LTD
Guangzhou, Guangdong, China
Zhujiang Hospital of Southern Medical University
Guanzhou, Guangdong, China
Overall response rate
A total number of patients achieved a Complete response (CR) or CR with incomplete blood count recovery (CRi) on Day 28 and three months by an independent review committee(IRC) assessment, as evaluated by peripheral blood, bone marrow, central nervous system (CNS) symptoms, physical exam (PE), and cerebrospinal fluid(CSF).
Time frame: 3 months
The maximum tolerated dose(MTD) of CAR19T2 T cells
The maximum tolerated dose(MTD) of CD19-positive relapsed/ refractory acute leukemia/lymphoma treated with CAR19T2 T cells.
Time frame: 24 weeks
Adverse Events (AEs)
Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups).
Time frame: 3 years
Minimal residual disease (MRD) negative response rate
Patients achieving CR or CRi and a negative MRD bone marrow.
Time frame: Up to 12 months after infusion
Event-free survival (EFS)
Time from CAR19T2 T cell infusion to progressive disease (PD), disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first.
Time frame: Up to 3 years after infusion
Overall survival (OS)
Time from CAR19T2 T cell infusion to time of death due to any cause.
Time frame: Up to 3 years after infusion
CAR-T cell expansion level
Copies numbers of CAR in peripheral blood (PB) and/or bone marrow (BM), CSF and lymph nodes, etc.
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Time frame: 24 months
The duration of CAR T cell persistence
The duration of CAR T cell persistence in peripheral blood(PB) and/or bone marrow(BM), CSF and lymph nodes, etc.
Time frame: 24 months
Rate of hematopoietic stem cell transplant (HSCT) after CAR19T2 T cell infusion
Percentage of subjects who achieve a response after CAR19T2 T cell infusion and then proceed to HSCT.
Time frame: Up to 3 years after CAR19T2 T infusion
Maximum concentration of CAR19T2 T cell and cytokines.
Pharmacokinetics of CAR19T2 T cell in Maximum concentration.
Time frame: 12 months
Time to peak concentration of CAR19T2 T cell and cytokines.
Pharmacokinetics of CAR19T2 T cell in Time to peak concentration.
Time frame: 12 months
Area under the curve of CAR19T2 T cell and cytokines.
Pharmacokinetics of CAR19T2 T cell in Area under the curve.
Time frame: 12 months
Incidence of hypogammaglobulinaemia
Incidence and duration of hypogammaglobulinaemia.
Time frame: 12 months