A randomized, open-label, controlled phase 3 study investigating the efficacy and safety of BITE® blinatumomab in adolescent and childern with high risk first relapse B-precursor ALL

Drug: Blinatumomab;Drug: Dexamethasone;Drug: Vincrisitne;Drug: Daunorubicin;Drug: Methotrexate;Drug: Ifosfamide;Drug: PEG-asparaginase;Drug: Erwinia-asparaginase

Gender: All
Maximum age: 17 Years
Minimum age: 0 Years

Inclusion Criteria:

- Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse
B-precursor acute lymphoblastic leukemia (ALL; as defined by International
Berlin-Frankfurt-Muenster study group/International study for treatment of childhood
relapsed ALL [I-BFM SG/IntReALL] criteria)

- Subjects with bone marrow blast percentage < 5% (M1) or bone marrow blast percentage <
25% and =5% (M2) marrow at the time of randomization,

- Age > 28 days and < 18 years at the time of informed consent/assent

- Subject's legally acceptable representative has provided informed consent when the
subject is legally too young to provide informed consent and the subject has provided
written assent based on local regulations and/or guidelines prior to any
study-specific activities/procedures being initiated

- Availability of the following material from relapse diagnosis for central analysis of
minimal residual disease (MRD) by polymerase chain reaction (PCR): clone-specific
primers and reference deoxyribonucleic acid (DNA), as well as primer sequences and
analyzed sequences of clonal rearrangements (cases with isolated extramedullary
relapse or cases with technical and/or logistic hurdles to obtain and process bone
marrow material are exempt from providing this material. In these cases, central MRD
analysis only by Flow is permitted).

Exclusion Criteria:

- Clinically relevant central nervous system (CNS) pathology requiring treatment (eg,
unstable epilepsy). Evidence of current CNS (CNS 2, CNS 3) involvement by ALL.
Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully
treated prior to enrollment

- Peripheral neutrophils < 500/?L prior to start of treatment

- Peripheral platelets < 50,000/?L prior to start of treatment

- Currently receiving treatment in another investigational device or drug study or less
than 4 weeks since ending treatment on another investigational device or drug
study(s), procedures required by IntReALL high-risk (HR) guidelines are allowed

- Chemotherapy related toxicities that have not resolved to = grade 2 (except for
parameters defined in Exclusion Criteria 202, 203, 204, and 217)

- Symptoms and/or clinical signs and/or radiological and/or sonographic signs that
indicate an acute or uncontrolled chronic infection, any other concurrent disease or
medical condition that could be exacerbated by the treatment or would seriously
complicate compliance with the protocol

- Abnormal renal or hepatic function prior to start of treatment (day 1) as defined
below

- Abnormal serum creatinine based on age/gender

- Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to Gilbert's
or Meulengracht disease)

- Documented infection with human immunodeficiency virus (HIV)

- Known hypersensitivity to immunoglobulins or any of the products or components to be
administered during dosing (excluding asparaginase)

- Post-menarchal female subject who is pregnant or breastfeeding, or is planning to
become pregnant or breastfeed while receiving protocol-specified therapy and for at
least 12 months after the last dose of chemotherapy

- Post-menarchal female subject who is not willing to practice true sexual abstinence or
use a highly effective form of contraception while receiving protocol-specified
therapy and for at least 12 months after the last dose of chemotherapy

- Sexually mature male subject who is not willing to practice true sexual abstinence or
use a condom with spermicide while receiving protocol-specified therapy and for at
least 6 months after last dose of chemotherapy. In countries where spermicide is not
available, a condom without spermicide is acceptable

- Sexually mature male subject who is not willing to abstain from sperm donation while
receiving protocol-specified therapy and for at least 6 months after last dose of
chemotherapy

- Subject likely to not be available to complete all protocol-required study visits or
procedures, including follow-up visits, and/or to comply with all required study
procedures to the best of the subject's and investigator's knowledge

- History or evidence of any other clinically significant disorder, condition or disease
(with the exception of those outlined above) that, in the opinion of the investigator
or Amgen physician, if consulted, would pose a risk to subject safety or interfere
with the study evaluation, procedures, or completion

- Placed into an institution due to juridical or regulatory ruling.