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

Overview

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

• Drug Blinatumomab
  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.
• Other Consolidation 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

Primary outcome measures

• 2-year Relapse-Free Survival (RFS) [Time frame: 2 years after transplantation]

Secondary outcome measures (5)

• Cumulative Incidence of Relapse (CIR) [Time frame: Up to 2 years after transplantation]
• Non-Relapse Mortality (NRM) [Time frame: Up to 2 years after transplantation]
• Incidence of Hematologic and Non-Hematologic Adverse Events [Time frame: From first dose of study drug to 100 days post-transplant]
• Measurable Residual Disease (MRD) Status [Time frame: From enrollment to up to 2 years after transplantation]
• 2-year Overall Survival (OS) [Time frame: 2 years after transplantation]

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:

• Clinical high-risk features (any of the following):

• Age > 35 years
• Peripheral WBC count > 30 × 10⁹/L
• Cytogenetic/molecular 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

• Prior exposure to blinatumomab, chimeric antigen receptor (CAR) T-cell therapy, or anti-CD22 immunotoxins.
• 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.
• Other severe comorbidities that may limit participation in the trial (e.g., severe infection, renal failure).
• Known HIV infection or uncontrolled severe viral hepatitis.
• Pregnant or breastfeeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07003737 · BLI4MRD-BALL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗