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

NCT07003737 | Recruiting

• 1 other identifier: BLI4MRD-BALL
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia, B-precursor

Keywords

allogeneic hematopoietic stem cell transplantation; measurable residual disease; Blinatumomab; high-risk BCR::ABL1-negative

Outcome Measures

Primary Outcomes (1)

• 2-year Relapse-Free Survival (RFS)

  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.

  2 years after transplantation

Secondary Outcomes (5)

• Cumulative Incidence of Relapse (CIR)

  Up to 2 years after transplantation

• Non-Relapse Mortality (NRM)

  Up to 2 years after transplantation

• Incidence of Hematologic and Non-Hematologic Adverse Events

  From first dose of study drug to 100 days post-transplant

• Measurable Residual Disease (MRD) Status

  From enrollment to up to 2 years after transplantation

• 2-year Overall Survival (OS)

  2 years after transplantation

Study Arms (2)

Control Group (Non-BiTE group)

SHAM COMPARATOR

Patients proceed directly to allo-HSCT without blinatumomab intensification.

Other: Consolidation Chemotherapy or Direct Allogeneic HSCT

Blinatumomab Group (BiTE group)

EXPERIMENTAL

Patients receive short-term blinatumomab intensification before undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Drug: Blinatumomab

Interventions

Blinatumomab DRUG

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.

Blinatumomab Group (BiTE group)

Consolidation Chemotherapy or Direct Allogeneic HSCT OTHER

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

Control Group (Non-BiTE group)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

blinatumomab; Consolidation Chemotherapy

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Central Study Contacts

Hengwei Wu Attending, MD

CONTACT

+8619858162455; wuhengwei@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director, Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 4, 2025
• Study Start: February 5, 2025
• Primary Completion (Estimated): February 5, 2027
• Study Completion (Estimated): February 5, 2028
• Last Updated: June 4, 2025

Record last verified: 2025-02

Locations

CN (1)