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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.
The CAR-T cells were murine-derived second-generation CD19 CAR-T with a co-stimulation domain of 4-1BB, and the infusion dose was 1×10^6/kg CAR+ cells in a single infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemotherapy and Sequential CAR-T Cells | Experimental | Ph-ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with pediatric-inspired regimen and venetoclax. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAR-T cells | Combination Product | CAR-T cells as consolidation therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free Survival (DFS) | From CR1 to relapse, death from any cause or last follow-up | Up to 2 years post-registration |
| Measure | Description | Time Frame |
|---|---|---|
| MRD-negative complete remission rate measured by flow cytometry. | No blasts were detected by flow cytometry when CR criteria were met after induction therapy. | After induction (4 week)] |
| Overall survival (OS) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jianxiang Wang, Dr | Contact | 86-22-23608451 | wangjx@ihcams.ac.cn |
| Name | Affiliation | Role |
|---|---|---|
| Jianxiang Wang, Dr | Institute of Hematology & Blood Diseases Hospital, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology & Blood Diseases Hospital | Recruiting | Tianjin | 300020 | China |
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| Venetoclax | Drug | VEN |
|
|
From the date of registration to the date of death resulting from any cause.
| Up to 5 years post-registration |
| Event-free survival (EFS) | From the date of registration to the date of induction failure, relapse, death from any cause, or last follow-up | Up to 5 years post-registration |
| MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements | No clonal IG/TR rearrangements were detected by NGS | Up to 1 year post-registration |
| Cumulative incidence of relapse (CIR) | Calculated with the cumulative incidence method, with death in patients who had a complete hematologic response as a competing risk. | Up to 2 years post-registration] |
| The rate of adverse events | adverse events during the treatment | Up to 5 years post-registration |
| From enrollment to 12 months |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D016219 | Immunotherapy, Adoptive |
| C579720 | venetoclax |
| D019254 | Genes, bcl-2 |
| ID | Term |
|---|---|
| D019264 | Adoptive Transfer |
| D007116 | Immunization, Passive |
| D007114 | Immunization |
| D007167 | Immunotherapy |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D011519 | Proto-Oncogenes |
| D009857 | Oncogenes |
| D052138 | Genes, Neoplasm |
| D005796 | Genes |
| D040481 | Genome Components |
| D016678 | Genome |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |
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