In recent years, immunotherapy (eg. blinatumomab, inotuzumab ozogamicin, CAR-T cells) has demonstrated a high safety and efficacy profile in relapsed/refractory (R/R）B-ALL. The available data suggest that the advancement of immunotherapy from relapsed/refractory (R/R) field to the frontline setting may be an important approach to increase the depth of remission, which ultimately translates into a survival benefit. In this study, the investigators propose a treatment regimen using CAR-T cell therapy as a consolidation method for Ph- B-ALL patients achieving complete remission (CR) with chemotherapy, aiming to reduce the total cycles of chemotherapy and related toxicities, shorten length of hospitalization, and ultimately improve patients' survival and quality of life.The study endpoints include 2-year disease-free survival (DFS) rate, overall survival (OS) rate, event-free survival (EFS) rate, cumulative molecular remission rate, immune repertoire-minimal residual disease (MRD) remission rate, cumulative relapse rate, treatment-related toxicities, and quality of life. Additionally, an interim analysis will be conducted, with the 1-year DFS rate as the key index for this analysis.
De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification
Male or female patients aged 18 years or older
CD19 expression on blasts
Expected survival time greater than 3 months
Burkitt lymphoma/leukemia
Acute Leukemia of Ambiguous Lineage
Clinical manifestations of active CNS or extramedullary involvement with ALL
Female patients who are pregnant or breast feeding
Single group
CAR-T cells
Combination productCAR-T cells as consolidation therapy
Venetoclax
DrugVEN
Disease-free Survival (DFS)
From CR1 to relapse, death from any cause or last follow-up
MRD-negative complete remission rate measured by flow cytometry.
No blasts were detected by flow cytometry when CR criteria were met after induction therapy.
Overall survival (OS)
From the date of registration to the date of death resulting from any cause.
Event-free survival (EFS)
From the date of registration to the date of induction failure, relapse, death from any cause, or last follow-up
MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements
No clonal IG/TR rearrangements were detected by NGS
Interim analysis index
It is planned to conduct one interim analysis in the study: when the median follow-up date of patients reaches 1 year, the Independent Data Monitoring Committee (IDMC) will perform a hypothesis test by comparing the 1-year disease-free survival (DFS) rate (the primary endpoint) of the trial group with the 70% 1-year DFS rate of the historical control. The alpha (α) spending function will be calculated using the O'Brien-Fleming method. If the DFS rate of the trial group is found to be significantly superior to that of the historical control in the interim analysis and achieves statistical significance at the nominal significance level αk, the trial may be terminated early. If no statistically significant difference is observed between the two groups in the interim analysis, the investigators will decide whether to continue the trial based on practical circumstances.
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