Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Adults with relapsed/refractory B-cell precursor ALL were randomized in a 2:1 ratio to
receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, SOC chemotherapy regimens.
Randomization was stratified by age (< 35 years vs ≥ 35 years of age), prior salvage therapy
(yes vs no), and prior allogeneic HSCT (yes vs no) as assessed at the time of consent.

The study consisted of up to a 3-week screening and pre-phase period, a treatment period
consisting of induction with 2 cycles of either blinatumomab or SOC chemotherapy, a
consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a
maintenance phase for up to an additional 12 months with protocol-specified therapy. A safety
follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term
follow-up period were included. The long-term follow-up part of the study was discontinued
prematurely based on a recommendation from the data monitoring committee (DMC) that the study
be stopped for benefit.

- 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.