Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CAR-T has been a major issue. Multi-antigen CAR T and combination with other regimens may reduce the relapse rate. The investigators first conducted CD22/CD19 CAR T-cells and auto-HSCT "sandwich " strategy as consolidation therapy in patients with B-ALL. The main Purpose of this study was to observe the safety and efficacy of this new strategy.
The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5\*10\^6/kg respectively,CAR-T1) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT(CAR-T2). Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5\*10\^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Modified BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGOverall survival (OS)
It is measured from the date of the first CAR-T (CAR-T 1) to the date of death from any cause; subjects not known to have died at last follow-up are censored on the date they were last known to be alive
Time frame: 2 years
Leukemia-free survival (LFS)
It is measured from the date of achievement of a remission after CAR-T 1 until the date of relapse from CR, or CRi, or death from any cause; subjects not known to have any of these events are censored on the date they were last examined.
Time frame: 2 years
Measurable residual disease (MRD) negative rate and duration
MRD is detected by flow cytometry (FC-MRD) and second-generation gene sequencing of IgH rearrangement (NGS-MRD) after the first CAR-T (CAR-T 1) . FC-MRD negative is defined as MRD\<10-4 and NGS-MRD negative is defined as MRD\<10-6.
Time frame: 2 years
Incidence of adverse events (AEs)
AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0) after the first CAR-T (CAR-T 1) .
Time frame: 2 years
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