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

Not Applicable

Recruiting

• Conditions: Acute Lymphoblastic Leukemia, B-precursor
• Interventions: Other: Consolidation Chemotherapy or Direct Allogeneic HSCT; Drug: Blinatumomab

• Registration Number: NCT07003737
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study Start: 2025-02-05
• Study First Submitted: 2025-05-27
• Study First Submitted QC: 2025-05-27
• Last Update Submitted: 2025-05-27
• Study First Posted: 2025-06-04
• Last Update Posted: 2025-06-04
• Primary Completion: 2027-02-05
• Study Completion: 2028-02-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 114

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:

3. 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):

4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group (Non-BiTE group)	Consolidation Chemotherapy or Direct Allogeneic HSCT	Patients proceed directly to allo-HSCT without blinatumomab intensification.
Blinatumomab Group (BiTE group)	Blinatumomab	Patients receive short-term blinatumomab intensification before undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

The First Affiliated Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China