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This is a prospective, multicenter, randomized controlled trial designed to evaluate whether short-term blinatumomab intensification before allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve survival outcomes in adults with high-risk BCR::ABL1-negative B-cell acute lymphoblastic leukemia (B-ALL) who have achieved measurable residual disease (MRD) negativity. Blinatumomab, a CD19/CD3 bispecific T-cell engager, has shown promising efficacy in eradicating MRD and prolonging survival in B-ALL patients. In this study, eligible participants will be randomly assigned to receive either short-term blinatumomab consolidation prior to allo-HSCT or proceed directly to allo-HSCT. The primary endpoint is relapse-free survival (RFS). This study aims to optimize treatment strategies and improve long-term outcomes for patients with high-risk BCR::ABL1-negative B-ALL.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group (Non-BiTE group) | Sham Comparator | Patients proceed directly to allo-HSCT without blinatumomab intensification. |
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| Blinatumomab Group (BiTE group) | Experimental | Patients receive short-term blinatumomab intensification before undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blinatumomab | Drug | Blinatumomab is administered starting approximately one month before allogeneic hematopoietic stem cell transplantation (allo-HSCT). For participants weighing ≥45 kg: 9 μg/day is administered on Days 1-3, followed by 28 μg/day on Days 4-14. For participants weighing <45 kg: 5 μg/m²/day (based on body surface area) is administered on Days 1-3, followed by 15 μg/m²/day on Days 4-14. The total dose must not exceed the dosage used for participants ≥45 kg. |
| Measure | Description | Time Frame |
|---|---|---|
| 2-year Relapse-Free Survival (RFS) | Relapse-free survival is defined as the time from transplantation to either disease relapse or death from any cause, whichever occurs first. Patients who are alive and relapse-free at 2 years will be considered as having achieved 2-year RFS. | 2 years after transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Relapse (CIR) | Defined as the cumulative incidence of hematologic relapse, accounting for competing risks such as non-relapse mortality. | Up to 2 years after transplantation |
| Non-Relapse Mortality (NRM) |
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Inclusion Criteria:
1. Diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) according to the 2022 WHO classification.
2. Age between 18 and 65 years. 3. Meets the National Comprehensive Cancer Network (NCCN) criteria for high-risk B-ALL, based on clinical or cytogenetic/molecular features:
Clinical high-risk features (any of the following):
Cytogenetic and molecular high-risk features (at least one of the following):
Hypodiploidy (<44 chromosomes)
TP53 mutation
KMT2A rearrangement
MLL rearrangement
HLF rearrangement
ZNF384 rearrangement
MEF2D rearrangement
MYC rearrangement
BCR-ABL1-like (Ph-like) ALL, including:
JAK pathway rearrangements (CRLF2r, EPORr, JAK1/2/3r, TYK2r, SH2B3 mutation, IL7R mutation, JAK1/2/3 mutations)
ABL-class rearrangements (ABL1, ABL2, PDGFRA, PDGFRB, FGFR1)
Other kinase fusions (e.g., NTRK3r, FLT3r, LYNr, PTK2Br)
PAX5alt
t(9;22)(q34.1;q11.2); BCR-ABL1 with IKZF1 mutation and/or prior chronic myeloid leukemia (CML)
Intrachromosomal amplification of chromosome 21 (iAMP21)
IKZF1 alteration
Complex karyotype (≥5 chromosomal abnormalities) 4. CD19-positive by immunophenotyping. 5. BCR::ABL1-negative. 6. Achieved complete remission (CR) after induction therapy. 7. Measurable residual disease (MRD)-negative by flow cytometry (FCM). 8. Availability of a matched sibling donor, haploidentical related donor, or matched/unmatched unrelated donor.
9. ECOG performance status score of 0-2. 10. Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault formula). 11. AST and ALT ≤ 3 × upper limit of normal (ULN); total bilirubin ≤ 2 × ULN. 12. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography. 13. Expected survival > 8 weeks. 14. Signed written informed consent, with ability to understand and comply with the study protocol.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hengwei Wu Attending, MD | Contact | +8619858162455 | wuhengwei@zju.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | 310000 | China |
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| Consolidation Chemotherapy or Direct Allogeneic HSCT | Other | Participants in the Non-BiTE group will either proceed directly to allogeneic hematopoietic stem cell transplantation (allo-HSCT) or receive one additional cycle of consolidation chemotherapy prior to |
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Death from any cause without prior hematologic relapse.
| Up to 2 years after transplantation |
| Incidence of Hematologic and Non-Hematologic Adverse Events | Safety evaluation based on CTCAE v5.0 criteria, including treatment-related cytopenias, infections, neurotoxicity, and other adverse events. | From first dose of study drug to 100 days post-transplant |
| Measurable Residual Disease (MRD) Status | MRD status assessed using multi-parameter flow cytometry or PCR prior to HSCT. Evaluated as MRD-negative or MRD-positive. | From enrollment to up to 2 years after transplantation |
| 2-year Overall Survival (OS) | Overall survival is defined as the time from HSCT to death from any cause. Patients alive at 2 years are considered to have achieved 2-year OS. | 2 years after transplantation |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D018365 | Neoplasm, Residual |
| 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 |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C510808 | blinatumomab |
| D060830 | Consolidation Chemotherapy |
| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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