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

Minimal Residual Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04604691
• Other study ID #: 20197007
• Status: Recruiting
• Phase: Phase 1
• Start date: February 18, 2022
• Est. completion date: December 2024

Study information

• Verified date: February 2022
• Source: Seoul National University Hospital
• Contact: Hyoung Jin Kang, MD
• Phone: +82-2-2072-3452
• Email: kanghj[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2024
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia, Lymphoid
• Minimal Residual Disease
• Neoplasm, Residual
• Pediatric ALL, B Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Amgen

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete MRD response status after 1 cycle of blinatumomab		28 Days
Secondary	Hematologic Relapse-Free Survival (RFS)		24 Months
Secondary	Overall Survival (OS)		24 Months