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

NCT ID: NCT07003737

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-05
• Study Completion Date: 2028-02-05

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control Group (Non-BiTE group)

Patients proceed directly to allo-HSCT without blinatumomab intensification.

Group Type: SHAM_COMPARATOR

Consolidation Chemotherapy or Direct Allogeneic HSCT

Intervention Type: 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

Blinatumomab Group (BiTE group)

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

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Yanmin Zhao

Vice Director, Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hengwei Wu Attending, MD

Role: CONTACT

wuhengwei@zju.edu.cn

+8619858162455

Facility Contacts

Hengwei Wu

Role: primary

wuhengwei@zju.edu.cn

19858162455

Other Identifiers

BLI4MRD-BALL

Identifier Type: -

Identifier Source: org_study_id