Efficacy of Short-course Blinatumomab for MRD Erradication in B-ALL

Efficacy of Short-course Blinatumomab in Patients with Detectable Measurable Residual Disease with Philadelphia Chromosome-negative B-cell Acute Lymphoblastyc Leukemia

Detectable measurable residual disease (MRD) is the most important prognostic factor for B-cell acute lymphoblastic leukemia (B-ALL) for overall survival (OS) and disease-free survival (DFS). Patients who are MRD positive and have no access to novel immunotherapies should receive an allogeneic hematopoietic stem cell transplantation (HSCT). Blinatumomab is considered a standard of care (SOC) for this group of patients, however, the ideal treatment dose for MRD is unknown as doses were adjusted from the relapsed/refractory setting. Preliminary data suggest short cycles of blinatumomab can also be effective in states of lower disease burden prior to transplant. Thus, the investigators are performing a phase 2 trial assessing 7 days of blinatumomab as a bridge to HSCT

Primary endpoint is assessing the MRD response following a short-course blinatumomab infusion in patients with B-ALL with complete response (CR) and have detectable MRD disease who are candidates for HSCT. Secondary endpoints include incidence of adverse events, OS, DFS, percentage of patients who receive HSCT, incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS)

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia; Measurable Residual Disease (MRD)
• Intervention / Treatment: Drug: Short course of blinatumomab

Detailed Description

During the proposed treatment, blinatumomab therapy will be assigned as follows:

Blinatumomab 17.5 mcg per day for 2 days, followed by blinatumomab 28 mcg per day for 5 days. Dexamethasone 20 mg will be applied one hour before starting dose.

The immunotherapy will be applied as a 24-hour continuous infusion. The scheduled appointments will be on the initial day of blinatumomab, when the patient will be discharged from hospital and evaluation will be performed on day 10 with bone marrow aspiration and MRD assessment trough next generation flow cytometry. The results will be given at the appointment on day 14, along with an assessment profile for HSCT.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andres Gomez-De Leon, Professor of Hematology; Phone Number: +528116089404; Email: drgomezdeleon@gmail.com

Study Locations

• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Recruiting
      • Hospital Universitario Dr. Jose E. Gonzalez
      • Contact: Andres Gomez De Leon, Professor of Hematology; Phone Number: +528116089404; Email: drgomezdeleon@gmail.com
      • Contact: David Gomez-Almaguer, Head of Hematology Service; Phone Number: +528182593389; Email: dgomezalmaguer@gmail.com
      • Contact: Andres Gomez De Leon, Proffesor of Hematology
      • Contact: David Gomez Almaguer, Head of Hematology Service
      • Contact: Luis P. Ugarte Pelaez, Fellow of Hematology
      • Contact: Francisco J Rubio Macias, Fellow of Hematology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia
• MRD detectable in complete response (above the limit of quantification according to FCM)
• Performance status 0-2 on the ECOG scale
• No prior organ damage
• Having a potential related or unrelated donor

Exclusion Criteria:

• Performance status on the ECOG scale >2
• HCT-CI >3 points
• Patients who do not wish to participate in clinical study.
• Active central nervous system infiltration (CNS3)
• Active extramedullary disease
• Having previously received blinatumomab
• Absence of related or unrelated donors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinatumomab arm; Patients will receive 7 days of blinatumomab with a fixed dose of 175 mcg through out 7 days	Drug: Short course of blinatumomab; Patients will receive 175 mcg of blinatumomab trough out seven days in a 24-hours infusion. Blinatumomab therapy will be assigned 17.5 mcg per day for the first 2 days. Then blinatumomab 28 mcg per day for 5 days (completing 7 days). A single intravenous 20 mg dose of dexamethasone will be applied one hour before starting dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy to eradicate MRD in negative Philadelphia-chromosome B-cell acute lymphoblastic leukemia	Primary outcome is to determinate the efficacy of blinatumomab to eradicate MRD in a blood sample extracted by bone marrow aspiration and evaluated by next generation flow cytometry on the third day after blinatumomab completion (day 10 after initiation). MRD eradication will be defined as: undetectable (below limit of detection) disease through next generation flow cytometry.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Survival time after enrollment	24 months
Disease free survival	Time from enrollment to relapse	24 months
Percentage of patients undergoing stem cell transplantation	Percentage of patients who undergo hematopoietic stem cell transplantation after enrollment	24 months
Incidence of adverse events	Incidence of hematologic (anemia, thrombocytopenia, leukopenia, neutropenia, lymphocytopenia) and non-hematologic (renal, hepatic, dermatologic, cardiovascular, infectious) adverse events after initiating blinatumomab therapy assessed by CTCAE V 5.0	24 months
Incidence of cytokine release syndrome	Incidence and grading of cytokine release syndrome after initiating blinatumomab through CTCAE V 5.0	24 months
Incidence of immune effector cell-associated neurotoxicity syndrome	Incidence and grading of immune effector cell-associated neurotoxicity syndrome after initiating blinatumomab assessed by ASTCT grading system.	24 months

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Publications and helpful links

General Publications

• Yin J, Cai X, Qian B, Liu Y, Li D. Short-Course Blinatumomab Treatment as a Bridge to Further Salvage Therapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Study. Cancer Med. 2024 Dec;13(24):e70515. doi: 10.1002/cam4.70515.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Blinatumomab; Measurable residual disease
• 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: HE25-00007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No