Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Condition: Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Blinatumomab; Standard of Care Chemotherapy
Intervention description: Blinatumomab is administered as a continuous intravenous infusion (CIV).; FLAG (fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor) ± anthracycline-based regimen (e.g. idarubicin 10 mg/m² days 1 & 3; fludarabine 30 mg/m² days 1-5; cytarabine arabinoside 2 g/m² days 1-5). Patients > 60 years: Idarubicin 5 mg/m² day 1 & 3; fludarabine 20 mg/m² day 1-5; cytarabine arabinoside 1 g/m² day 1-5
HiDAC (high-dose cytarabine arabinoside) - based regimen ≥1 g/m²/day ± anthracycline and/or in combination with other drugs such as native Escherichia coli asparaginase, polyethylene glycol linked to asparaginase (PEG-asparaginase), vinca alkaloids, steroids, etoposide or alkylating agents
High-dose methotrexate-based regimen (HDMTX; 500 mg/m² to 3 g/m² infused up to 24 hours) in combination with native E. coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents.
Clofarabine as a single agent as recommended in the prescribing information or clofarabine-based regimens with 20 mg/m²/day for up to 5 days.
Intervention MeSH terms: Blinatumomab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 405.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC

Summary:

      The primary objective was to evaluate the effect of blinatumomab on overall survival when
      compared to standard of care (SOC) chemotherapy.
    

Eligibility criteria:

        -  Subjects with Philadelphia negative B-precursor ALL, with any of the following:

               -  refractory to primary induction therapy or refractory to salvage therapy,

               -  in untreated first relapse with first remission duration <12 months

               -  in untreated second or greater relapse

               -  relapse at any time after allogeneic HSCT

          -  Subject has received intensive combination chemotherapy for the treatment of ALL for
             initial treatment or subsequent salvage therapy.

          -  Greater than 5% blasts in the bone marrow

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

        Exclusion Criteria

          -  Malignancy other than ALL within 5 years before blinatumomab treatment, except for
             adequately treated selected cancers without evidence of disease

          -  Diagnosis of Burkitt's leukemia according to World Health Organization classification,
             or human immunodeficiency virus (HIV), Hepatitis B or C, or other clinically
             significant disorder

          -  Current relevant central nervous system (CNS) pathology or known or suspected CNS
             involvement

          -  Isolated extramedullary disease

          -  Current autoimmune disease or history of autoimmune disease with potential CNS
             involvement

          -  Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab
             treatment, or eligibility for allogeneic HSCT at the time of enrollment

          -  Active acute grade 2 to 4 graft versus host disease (GvHD) according to Glucksberg et
             al (1974) criteria that required systemic treatment to prevent or treat GvHD 2 weeks
             before blinatumomab treatment

          -  Known exclusion criteria to investigator choice of SOC chemotherapy (per package
             insert)

          -  Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19
             therapy) within 4 weeks of protocol-specified therapy

          -  Abnormal laboratory values (alanine or aspartate transaminase [ALT or AST] or alkaline
             phosphatase [ALP] ≥ 5 × upper limit of normal [ULN]; total bilirubin or creatinine ≥
             1.5 × ULN), or calculated creatinine clearance < 60 mL/min.