Minimal Residual Disease, Pediatric ALL, B Cell
Conditions
Brief 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.
Interventions
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.
Sponsors
Amgen
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety evaluation including cytokine release syndrome | At the latest possible timepoint prior to the initiation of transplant conditioning or after 30 days of Blinatumomab treatment | The incidence of treatment-emergent and treatment-related adverse events |
Secondary
| 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 |
Countries
South Korea
Contacts
Primary ContactHyoung Jin Kang, MD
Outcome results
None listed