Primary Objectives:
To assess the Efficacy of Brexucabtagene autoleucel \[anti-CD19 autologous derived chimeric antigen receptor T-cell (CAR-T)\] in terms of EFS in patients with R/R and high-risk newly diagnosed B-cell acute lymphoblastic leukemia (B-cell ALL) post cytoreduction with mini-hyper-CVD-inotuzumab-blinatumomab/Hyper-CVAD-inotuzumab-blinatumomab
The EFS will be estimated in terms of median EFS and 9-month EFS for the R/R cohort and 18-month EFS for the frontline cohort.
Secondary Objectives:
1. 12 and 24-months overall survival (OS): 12 months for the R/R cohort and 24 months for the frontline cohort
2. Duration of persistent MRD negativity by flow cytometry and NGS at 9 and 18 months: 9 months for the R/R cohort and 18 months for the frontline cohort
3. Best Ooverall response rates \[complete remission (CR) and CR with incomplete count recovery (CRi)\]
4. Achievement of MRD negativity amongst patients in CR and not MRD negative before Brexucabtagene autoleucel infusion
5. Safety
Exploratory Objectives:
1. CAR-T-cell expansion ((Days 1, 4, 8, 11, 14, 21, 28, monthly up to 3 months and then every 3 months up to 24 months post infusion)
2. B-cell aplasia (Days 0, 7, 14, 28, monthly up to 3 months and then every 3 months up to 24 months post infusion)
3. Measurable residual disease (MRD) negativity by next-generation sequencing (NGS) (at 1 in 105-6 sensitivity) (PB on D14 and PB/BM: Day 28, and then Q3 months up to 24 months post infusion)
4. Cytokine panel (Days 0, 1, 2, 4, 7, 10, 14, 28)
5. Additional correlatives samples to address tumor samples and immune system factors will be collected at baseline, D28 and Q3 months. These include samples for bulk RNA sequencing of the tumor and germline and single cell RNA sequencing of CAR T-cells as also for assessing the methylation signatures of the CAR T-cells.
