NGS MRD-Guided Blinatumomab Treatment for Pediatric B-ALL

The goal of this clinical trial is to determine whether pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients with negative deep minimal residue disease (MRD) can benefit from blinatumomab treatment.

The main questions it aims to answer are:

1. Whether the application of blinatumomab can improve the long-term survival of next generation sequence (NGS) MRD-positive B-ALL children after consolidation therapy?
2. Whether the application of blinatumomab can benefit the NGS MRD-negative B-ALL children after consolidation therapy?

Study Overview

• Status: Not yet recruiting
• Conditions: Minimal Residual Disease; Pediatric; B Cell Precursor Acute Lymphoblastic Leukemia; Next Generation Sequencing (NGS)
• Intervention / Treatment: Drug: Blinatumomab

• Study Type: Interventional
• Enrollment (Estimated): 1220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaojun Xu; Phone Number: +86-571-88873450; Email: xuxiaojun@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clincial dianogsis of acute lymphoblastic leukemia (B-cell type) by morphology, immunology, cytogenetics, and molecular biology (MICM).
• Age ≥1 year and <18 years.
• Informed consent signed, with the parents or guardians agreeing to a unified treatment protocol.

Exclusion Criteria:

• Age <1 year or ≥18 years.
• Immunophenotyping suggests mature B-cell leukemia, mixed-lineage leukemia, or T-cell acute lymphoblastic leukemia.
• Secondary leukemia or second tumor, CML blast phase ALL.
• Other tumors or immunodeficiency diseases present.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EOC NGS MRD positive Group; Based on the B-ALL treatment protocol, NGS MRD levels will be monitored at the end of consolidation treatment (EOC). If NGS MRD is positive (≥0.0001%), one course of blinatumomab (28 days) will be added after the consolidation treatment.	Drug: Blinatumomab; The FDA has approved blinatumomab for post-consolidation treatment in all Ph-negative B-ALL cases, regardless of MRD status. Considering the high cost of blinatumomab and the financial burden on families, we aim to precisely identify the population who would benefit from blinatumomab and provide appropriate treatment.
Active Comparator: EOC NGS MRD negative Group A; Based on the B-ALL treatment protocol, NGS MRD levels will be monitored at the end of consolidation treatment (EOC). If NGS MRD is negative (< 0.0001%), the IR/HR patients will be randomized into A and B two groups. EOC NGS MRD negative Group A will be added by one course of blinatumomab (28 days) treatment after the consolidation treatment.	Drug: Blinatumomab; The FDA has approved blinatumomab for post-consolidation treatment in all Ph-negative B-ALL cases, regardless of MRD status. Considering the high cost of blinatumomab and the financial burden on families, we aim to precisely identify the population who would benefit from blinatumomab and provide appropriate treatment.
No Intervention: EOC NGS MRD negative Group B; Based on the B-ALL treatment protocol, NGS MRD levels will be monitored at the end of consolidation treatment (EOC). If NGS MRD is negative (< 0.0001%), the IR/HR patients will be randomized into A and B two groups. EOC NGS MRD negative Group B will continue the original chemotherapy treatment plan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event free survival	Death during induction, abandonment before complete remission, death in continuous complete remission, relapse, and secondary Death during induction, abandonment before complete remission (CR), death in continuous complete remission (CCR), relapse, and secondary malignancies were considered as events in the calculation of EFS probability.	From enrollment to the 3-year after the end of treatment
Relapse free survival	RFS was measured by the time from achievement of CR to last follow-up or first relapse and censored at the first event (death, secondary malignancies) except relapse.	From enrollment to the 3-year after the end of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Treatment-Related Adverse Events as Assessed by CTCAE v4.0	From enrollment to the 3-year after the end of treatment

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Publications and helpful links

General Publications

• Chen H, Gu M, Liang J, Song H, Zhang J, Xu W, Zhao F, Shen D, Shen H, Liao C, Tang Y, Xu X. Minimal residual disease detection by next-generation sequencing of different immunoglobulin gene rearrangements in pediatric B-ALL. Nat Commun. 2023 Nov 17;14(1):7468. doi: 10.1038/s41467-023-43171-9.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: 2024-IRB-0307-P-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No