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RecruitingNot ApplicableNCT07003737

Blinatumomab Intensification for MRD-Negative Acute B-Cell Lymphoblastic Leukemia Before Allogeneic Hematopoietic Stem Cell Transplantation

Short-term Blinatumomab Intensification for MRD-Negative Acute B-Cell Lymphoblastic Leukemia Before Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective, Multicenter, Randomized Controlled Study

Sponsor

First Affiliated Hospital of Zhejiang University

Enrollment

114 participants

Start Date

Feb 5, 2025

Study Type

INTERVENTIONAL

Conditions

Acute Lymphoblastic Leukemia, B-precursor

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

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria25

  • \. Diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) according to the 2022 WHO classification.
  • \. 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.
  • \. 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 Criteria5

  • 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.

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

Locations(1)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

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NCT07003737