Acute Lymphoblastic Leukemia, B-precursor
Conditions
Keywords
allogeneic hematopoietic stem cell transplantation, measurable residual disease, Blinatumomab, high-risk BCR::ABL1-negative
Brief summary
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.
Interventions
DRUGBlinatumomab
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.
OTHERConsolidation Chemotherapy or Direct Allogeneic HSCT
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
Sponsors
First Affiliated Hospital of Zhejiang University
Ruijin Hospital
The First Affiliated Hospital of Zhengzhou University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
The Children's Hospital of Zhejiang University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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: 1. Clinical high-risk features (any of the following): 1. Age \> 35 years 2. Peripheral WBC count \> 30 × 10⁹/L 3. Cytogenetic/molecular high-risk features (any of the following): 2. Cytogenetic and molecular high-risk features (at least one of the following): 1. Hypodiploidy (\<44 chromosomes) 2. TP53 mutation 3. KMT2A rearrangement 4. MLL rearrangement 5. HLF rearrangement 6. ZNF384 rearrangement 7. MEF2D rearrangement 8. MYC rearrangement 9. BCR-ABL1-like (Ph-like) ALL, including: 10. JAK pathway rearrangements (CRLF2r, EPORr, JAK1/2/3r, TYK2r, SH2B3 mutation, IL7R mutation, JAK1/2/3 mutations) 11. ABL-class rearrangements (ABL1, ABL2, PDGFRA, PDGFRB, FGFR1) 12. Other kinase fusions (e.g., NTRK3r, FLT3r, LYNr, PTK2Br) 13. PAX5alt 14. t(9;22)(q34.1;q11.2); BCR-ABL1 with IKZF1 mutation and/or prior chronic myeloid leukemia (CML) 15. Intrachromosomal amplification of chromosome 21 (iAMP21) 16. IKZF1 alteration 17. 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
1. Prior exposure to blinatumomab, chimeric antigen receptor (CAR) T-cell therapy, or anti-CD22 immunotoxins. 2. Clinically significant cardiovascular disease, including uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, NYHA class III or IV heart disease, or myocardial infarction within 3 months prior to screening. 3. Other severe comorbidities that may limit participation in the trial (e.g., severe infection, renal failure). 4. Known HIV infection or uncontrolled severe viral hepatitis. 5. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year Relapse-Free Survival (RFS) | 2 years after transplantation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Relapse (CIR) | Up to 2 years after transplantation | Defined as the cumulative incidence of hematologic relapse, accounting for competing risks such as non-relapse mortality. |
| Non-Relapse Mortality (NRM) | Up to 2 years after transplantation | Death from any cause without prior hematologic relapse. |
| Incidence of Hematologic and Non-Hematologic Adverse Events | From first dose of study drug to 100 days post-transplant | Safety evaluation based on CTCAE v5.0 criteria, including treatment-related cytopenias, infections, neurotoxicity, and other adverse events. |
| Measurable Residual Disease (MRD) Status | From enrollment to up to 2 years after transplantation | MRD status assessed using multi-parameter flow cytometry or PCR prior to HSCT. Evaluated as MRD-negative or MRD-positive. |
| 2-year Overall Survival (OS) | 2 years after transplantation | 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. |
Countries
China
Contacts
CONTACTHengwei Wu Attending, MD
Outcome results
None listed