Blinatumomab before allogeneic stem cell transplant for MRD‑negative high‑risk B‑cell ALL

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

This test sees if a short course of blinatumomab given before an allogeneic stem cell transplant helps adults (18–65) with high‑risk, BCR::ABL1‑negative B‑cell ALL who are MRD‑negative to lower relapse and improve survival.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 114 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (other)
• Drugs / interventions: blinatumomab, chimeric antigen receptor
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07003737 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized trial enrolling adults with high‑risk, BCR::ABL1‑negative B‑cell acute lymphoblastic leukemia who have achieved measurable residual disease (MRD) negativity and are planned for allogeneic hematopoietic stem cell transplantation (allo‑HSCT). Eligible participants are randomized to receive a short course of blinatumomab consolidation prior to allo‑HSCT or to proceed directly to allo‑HSCT. Blinatumomab is a CD19/CD3 bispecific T‑cell engager previously shown to clear MRD in B‑ALL; the trial's primary endpoint is relapse‑free survival. The goal is to determine whether pre‑transplant intensification with blinatumomab improves long‑term outcomes compared with immediate transplantation.

Who should consider this trial

Good fit: Adults aged 18–65 with high‑risk, BCR::ABL1‑negative B‑cell ALL who have achieved MRD negativity and are planned to undergo allogeneic HSCT are the ideal candidates.

Not a fit: Patients with BCR::ABL1‑positive disease, persistent MRD positivity, major comorbidities that preclude blinatumomab or transplant, or those outside the age range are unlikely to benefit from this specific approach.

Why it matters

Potential benefit: If successful, adding short‑term blinatumomab before transplant could reduce relapse rates and improve long‑term survival after allo‑HSCT for high‑risk MRD‑negative B‑ALL patients.

How similar studies have performed: Prior studies have shown blinatumomab can eradicate MRD and improve outcomes in B‑ALL, but randomized data specifically testing short pre‑transplant blinatumomab intensification are limited.

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.

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Hengwei Wu Attending, MD

Conditions: Acute Lymphoblastic Leukemia, B-precursor, allogeneic hematopoietic stem cell transplantation, measurable residual disease, Blinatumomab, high-risk BCR::ABL1-negative