Clinical trial NCT02393859 (phase 3, status: active, not recruiting)
Conditions: leukemia, acute lymphoblastic
ICD codes: C91.01, C91.02, C91.00
Drugs: blinatumomab, dexamethasone, vincrisitne, daunorubicin, methotrexate, ifosfamide, peg-asparaginase, erwinia-asparaginase
SMILES: C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(C)=O)C(O)=C1C2=O, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, N[C@@H](CCCNC(N)=N)C(O)=O
Eligibility criteria:

        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

          -  Abnormal renal or hepatic function prior to start of treatment (day 1) as defined
             below: a. Serum creatinine levels above upper limit of normal, based on the normal
             ranges for age and gender of the local laboratories. b. Total bilirubin > 3.0 mg/dL
             prior to start of treatment (unless related to Gilbert's or Meulengracht disease)

          -  Peripheral neutrophils < 500/μL prior to start of treatment

          -  Peripheral platelets < 50,000/μL 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, and 204)

          -  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

          -  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 6 months after the last dose of blinatumomab or for 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 6 months after the last dose of blinatumomab or for 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 thereafter. 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 thereafter

          -  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.