A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia

Inclusion Criteria:

   - All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening
   (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement
   for B-LLy patients. B-LLy patients may directly enroll on AALL1731.

   - Age at diagnosis:

      - Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).

      - Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).

      - Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or
      without DS).

   - B-ALL patients without DS must have an initial white blood cell count < 50,000/uL
   (performed within 7 days prior to enrollment).

   - B-ALL patients with DS are eligible regardless of the presenting white blood cell
   count (WBC) (performed within 7 days prior to enrollment).

   - Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on
   a bone marrow (BM) aspirate;

      - OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis
      can be established by a pathologic diagnosis of B-ALL on a BM biopsy;

      - OR a complete blood count (CBC) documenting the presence of at least 1,000/uL
      circulating leukemic cells;

      - OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without
      Down syndrome.

      - Note: For B-LLy patients with tissue available for flow cytometry, the criterion
      for diagnosis should be analogous to B-ALL. For tissue processed by other means
      (i.e., paraffin blocks), the methodology and criteria for immunophenotypic
      analysis to establish the diagnosis of B-LLy defined by the submitting
      institution will be accepted (diagnostic biopsy for B-LLy must be performed
      within 14 days prior to enrollment).

   - All patients and/or their parents or legal guardians must sign a written informed
   consent.

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met.

Exclusion Criteria:

   - Patient must not have secondary ALL that developed after treatment of a prior
   malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior
   history of transient myeloproliferative disease (TMD) are not considered to have had a
   prior malignancy. They would therefore be eligible whether or not the TMD was treated
   with cytarabine.

   - With the exception of steroid pretreatment or the administration of intrathecal
   cytarabine, patients must not have received any prior cytotoxic chemotherapy for
   either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to
   initiation of protocol therapy on AALL1731.

   - For patients receiving steroid pretreatment, the following additional exclusion
   criteria apply:

      - Non-DS B-ALL patients must not have received steroids for more than 24 hours in
      the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to
      initiation of the steroids.

      - DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV
      steroids within 4 weeks of diagnosis.

   - Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to
   the start of systemic protocol therapy.

   - B-ALL patients who do not have sufficient diagnostic bone marrow submitted for
   APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted
   containing > 1,000/uL circulating leukemia cells.

   - Patient must not have acute undifferentiated leukemia (AUL).

   - Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be
   known prior to enrollment).

      - Note: DS patients with CNS3 disease are eligible but will be assigned to the
      DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior
      to administration of any systemic or intrathecal chemotherapy, except for steroid
      pretreatment.

   - Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular
   disease are eligible but will be assigned to the DS-High B-ALL arm).

   - For LLy patients, the following additional exclusion criteria apply:

      - T-Lymphoblastic Lymphoma.

      - Morphologically unclassifiable lymphoma.

      - Absence of both B-cell and T-cell phenotype markers in a case submitted as
      lymphoblastic lymphoma.

      - CNS positive disease or testicular involvement.

      - M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.

   - Patients with known Charcot-Marie-Tooth disease.

   - Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
   regardless of blast immunophenotype.

   - Patients requiring radiation at diagnosis.

   - Female patients who are pregnant since fetal toxicities and teratogenic effects have
   been noted for several of the study drugs. A pregnancy test is required for female
   patients of childbearing potential.

   - Lactating females who plan to breastfeed their infants.

   - Sexually active patients of reproductive potential who have not agreed to use an
   effective contraceptive method for the duration of their study participation.