Clinical trial NCT07003737: Blinatumomab Intensification for MRD-Negative Acute B-Cell Lymphoblastic Leukemia Before Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Short-term Blinatumomab Intensification for MRD-Negative Acute B-Cell Lymphoblastic Leukemia Before Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective, Multicenter, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Lymphoblastic Leukemia, B-precursor
Keywords: allogeneic hematopoietic stem cell transplantation
measurable residual disease
Blinatumomab
high-risk BCR::ABL1-negative
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2025-06-04
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 2-year Relapse-Free Survival (RFS)
timeFrame: 2 years after transplantation
Secondary outcomes:
measure: Cumulative Incidence of Relapse (CIR)
timeFrame: Up to 2 years after transplantation
measure: Non-Relapse Mortality (NRM)
timeFrame: Up to 2 years after transplantation
measure: Incidence of Hematologic and Non-Hematologic Adverse Events
timeFrame: From first dose of study drug to 100 days post-transplant
measure: Measurable Residual Disease (MRD) Status
timeFrame: From enrollment to up to 2 years after transplantation
measure: 2-year Overall Survival (OS)
timeFrame: 2 years after transplantation
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: