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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pediatric ALL, B Cell, Minimal Residual Disease

Intervention / Treatment
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* Drug: Blinatumomab for Injection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinatumomab Treatment<br> | Drug: Blinatumomab for Injection<br>* 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.<br>|

What is the study measuring?
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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 | Measure Description | 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 |