PRIMARY OBJECTIVE:

      I. To evaluate the clinical efficacy of the sequential combination of hyperfractionated
      cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone
      (hyper-CVAD) + blinatumomab + inotuzumab ozogamicin (inotuzumab) in patients with newly
      diagnosed B-cell acute lymphoblastic leukemia (ALL) in terms of relapse-free survival (RFS).

      SECONDARY OBJECTIVE:

      I. To evaluate other efficacy endpoints such as overall survival, overall response rate,
      minimal residual disease (MRD) negativity rate as well as the safety of this combination.

      EXPLORATORY OBJECTIVES:

      I. To identify genomic alterations in adult ALL predictive for response and long-term
      outcomes with the combination of hyper-CVAD plus blinatumomab and inotuzumab.

      II. To evaluate the impact of next generation sequencing (NGS)-based MRD assay on outcomes
      and to compare with standard flow cytometry MRD assays.

      OUTLINE:

      INTENSIVE PHASE: Patients receive cyclophosphamide intravenously (IV) over 3 hours twice
      daily (BID) on days 1-3, dexamethasone orally (PO) once daily (QD) on days 1-4 and 11-14,
      methotrexate intrathecally (IT) on day 2 of cycles 1 and 3, day 8 of cycles 2 and 4, and IV
      over 24 hours on day 1 of cycles 2 and 4, doxorubicin hydrochloride IV continuously on day 4,
      vincristine sulfate IV over 15 minutes on days 4 and 11, and cytarabine IT on day 7 of cycles
      1 and 3, day 5 of cycles 2 and 4, and IV over 2 hours on days 2 and 3 of cycles 2 and 4.
      Patients may also receive ofatumumab IV or rituximab IV over 4-6 hours on days 1 and 11 of
      cycles 1 and 3, and days 1 and 8 of cycles 2 and 4 at the discretion of the treating
      physician. Patients may receive ofatumumab IV over 4-6 hours on day 2 of cycle 1. Treatment
      repeats every 3 weeks for up to 4 cycles in the absence of disease progression or
      unacceptable toxicity.

      BLINATUMOMAB AND INOTUZUMAB OZOGAMICIN PHASE (CYCLES 5-8): Patients receive blinatumomab IV
      continuously on weeks 1-4. Patients also receive inotuzumab ozogamicin IV over 1 hour on days
      5 and 11 of cycles 6 and 8. Treatment repeats every 6 weeks for up to 4 cycles in the absence
      of disease progression or unacceptable toxicity.

      MAINTENANCE PHASE: At doctor's discretion, patients may receive maintenance therapy prior to
      completing 4 cycles of hyper-CVAD and/or 4 cycles of blinatumomab. Patients receive
      mercaptopurine PO thrice daily (TID), methotrexate PO every week, vincristine sulfate IV over
      15 minutes every month, and prednisone PO on days 1-5. Cycles repeat every 6 weeks for 12
      months in the absence of disease progression or unacceptable toxicity. Patients also receive
      blinatumomab IV after every 3 cycles of maintenance therapy for a total of about 15 cycles.

      After completion of study treatment, patients are followed up 1 time each month for up to 24
      months.