Blinatumomab in Pediatric B-cell Acute Lymphoblastic Leukemia (ALL) With Minimal Residual Disease (MRD)

Blinatumomab for Minimal Residual Disease Before Hematopoietic Stem Cell Transplantation With Pediatric B-cell Precursor Acute Lymphoblastic Leukemia

This is a single-arm, open-label, multi-center phase I study using blinatumomab for pediatric B-cell acute lymphoblastic leukemia patients with positive of minimal residual disease. 1 Cycle of blinatumomab treatment followed by hematopoietic stem cell transplantation. Blinatumomab has approved to treat adults and children with B-cell precursor ALL who are in remission but still have MRD. However, data on the effects and safety of blinatumomab in children with B-precursor ALL with MRD positive are insufficient.

Study Overview

• Status: Recruiting
• Conditions: Minimal Residual Disease; Pediatric ALL, B Cell
• Intervention / Treatment: Drug: Blinatumomab for Injection

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Immunophenotypic evidence of Cluster of Differentiation 19 (CD19) positive B precursor ALL
• Age <18 years at the time of informed consent/assent
• B cell precursor ALL in first or later hematologic complete remission (CR) defined as less than 5% blasts in bone marrow after at least three intense chemotherapy blocks
• Persistent or recurrent MRD ≥10^-4 in an assay with a minimum sensitivity of 10^-5 before hematopoietic stem cell transplantation
• Bone marrow function as defined below: Absolute neutrophil count ≥1,000/μL, Platelets ≥50,000/μL (transfusion permitted), Hemoglobin level ≥9 g/dL (transfusion permitted)
• Renal and hepatic function as defined below: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and alkaline phosphatase (AP) < 2 x upper limit of normal (ULN), Total bilirubin <1.5 x ULN, Creatinine clearance ≥ 50 mL/min
• Negative HIV test, negative hepatitis B (HBsAg) and hepatitis C virus (anti-HCV) test
• Negative pregnancy test in women of childbearing potential

Exclusion Criteria:

• Presence of circulating blasts or current extramedullary involvement by ALL
• History of relevant central nervous system (CNS) pathology or current relevant CNS pathology (e.g. seizure, epilepsy, paresis, aphasia, stroke, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis) with the except of CNS leukemia that is well controlled with intrathecal therapy
• Current infiltration of cerebrospinal fluid by ALL
• History of or active relevant autoimmune disease
• Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
• Radiotherapy within 4 weeks prior to study treatment
• Autologous hematopoietic stem cell transplantation (HSCT) within six weeks prior to study treatment
• Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment
• Treatment with any investigational product within 4 weeks prior to study treatment
• Known hypersensitivity to immunoglobulin or to any other component of the study drug formulation
• Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
• Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator

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 Treatment	Drug: Blinatumomab for Injection; Blinatumomab will be administered as a continuous intravenous (CIV) infusion at a constant flow rate over four weeks followed by a two-week infusion free interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation including cytokine release syndrome	The incidence of treatment-emergent and treatment-related adverse events	At the latest possible timepoint prior to the initiation of transplant conditioning or after 30 days of Blinatumomab treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Complete MRD response status after 1 cycle of blinatumomab	28 Days
Hematologic Relapse-Free Survival (RFS)	24 Months
Overall Survival (OS)	24 Months

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Amgen

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: February 20, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplastic Processes; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasm, Residual; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: 20197007

Drug and device information, study documents

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