PRIMARY OBJECTIVES:

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

      SECONDARY OBJECTIVES:

      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.

      OUTLINE:

      INTENSIVE CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 3 hours
      every 12 hours on days 1-3 and dexamethasone IV or orally (PO) on days 1-4 and 11-14 of
      courses 1 and 3. Patients may receive ofatumumab IV over 2 hours on days 1, 2 and 11 of
      course 1, days 1 and 8 of courses 2 and 4, and days 1 and 11 of course 3, or rituximab IV
      over 2 hours on days 1 and 11 of courses 1 and 3, and days 1 and 8 of courses 2 and 4.
      Patients also receive methotrexate intrathecally (IT) on day 2 of courses 1 and 3, IV over 24
      hours on day 1 and IT on day 8 of courses 2 and 4, doxorubicin hydrochloride IV over 24 hours
      on day 4 of courses 1 and 3, vincristine sulfate IV over 1 hour on days 4 and 11 of courses 1
      and 3, cytarabine IT on day 7 of courses 1 and 3, and IV over 2 hours every 12 hours on days
      2 and 3, and IT on day 5 of courses 2 and 4, leucovorin calcium IV 4 times a days on day 2 of
      courses 2 and 4. Patients then receive inotuzumab ozogamicin IV over 1 hour on days 1 and 8
      of courses 5-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease
      progression or unacceptable toxicity.

      MAINTENANCE THERAPY: Patients receive mercaptopurine PO thrice a day, methotrexate PO once a
      week, vincristine sulfate IV over 1 hour on day 1 and prednisone PO on days 1-5. Treatment
      repeats every 28 days for up to 12 courses in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and every 6 months.