Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
Condition: Leukemia, Acute Lymphoblastic
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
Study type: Interventional
Phase: Phase 3

Summary: 
      B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according
      to risk characteristics to ensure that appropriate treatment is administered to patients with
      high-risk of relapse. In general, pediatric treatment regimens are more intense than those
      employed in adults and include courses of combination chemotherapy. Standard of care
      chemotherapy is associated with considerable toxicity. There is a lack of novel treatment
      options for subjects who relapse or are refractory to treatment. Therefore, innovative
      therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain
      antibody construct designed to link B cells and T cells resulting in T cell activation and a
      cytotoxic T cell response against CD19 expressing cells. This study will evaluate the
      event-free survival (EFS) after treatment with blinatumomab when compared to standard of care
      (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal
      residual disease compared to SOC chemotherapy will also be investigated.
    

Detailed description: 
      Patients will be randomized in a 1:1 ratio to receive either one cycle of blinatumomab or one
      block of standard high-risk consolidation chemotherapy. Blinatumomab is administered as a
      continuous intravenous infusion (CIVI). One cycle of blinatumomab treatment includes 4 weeks
      of CIVI of blinatumomab. After completing consolidation therapy, the patients should undergo
      alloHSCT depending on their bone marrow status. The patients will be followed up until the
      last subject on study is 36 months following alloHSCT or has died, whichever is first.
    

Intervention name(s): Blinatumomab; Dexamethasone; Vincrisitne; Daunorubicin; Methotrexate; Ifosfamide; PEG-asparaginase; Erwinia-asparaginase
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks; 10 mg/m^2/day intravenous (IV) on Days 1-6; 1.5 mg/m^2/day IV on Days 1 and 6; 30 mg/m^2 IV over 24 hours on Day 5; 1 g/m^2 IV over 36 hours on Day 1; 800 mg/m^2 IV for 1 hour on Days 2-4; 1000 U/m^2 IV for 2 hours or intramuscularly (IM) on Day 6; In case of allergic reaction to PEG-asparaginase, participants could change to erwinia-asparaginase, 20,000 units/m2 every 48 hours for a total of 6 doses
Other intervention name(s): Blincyto, AMG103
Intervention MeSH terms: Dexamethasone; Methotrexate; Daunorubicin; Asparaginase; Ifosfamide; Blinatumomab; Pegaspargase
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ALL; High-risk first relapse B-precursor ALL; Precursor Cell Lymphoblastic Leukemia; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Antibodies, Bispecific