PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in combination with
      low-intensity chemotherapy in elderly patients (age 60 or older) with acute lymphoblastic
      leukemia (ALL). (Phase I) II. Evaluate the efficacy of inotuzumab ozogamicin in combination
      with low-intensity chemotherapy in elderly patients with ALL. (Phase II) III. To evaluate the
      side effects of the treatment. (Phase II) IV. Evaluate the regimen efficacy in
      refractory-relapsed ALL. (Phase II)

      EXPLORATORY OBJECTIVES:

      I. To identify genomic alterations in adult ALL predictive for response and long-term
      outcomes with the combination of hyper-CVD (cyclophosphamide, dexamethasone, methotrexate,
      and cytarabine) + inotuzumab + blinatumomab.

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

      OUTLINE: This is a phase I, dose-escalation study of inotuzumab ozogamicin followed by a
      phase II study.

      CYCLES 1, 3, 7, AND 9: Patients receive cyclophosphamide intravenously (IV) over
      approximately 3 hours twice daily (BID) on days 1-3; vincristine sulfate IV over 30 minutes
      on days 1 and 8; inotuzumab ozogamicin IV over approximately 1 hour on day 3 of cycle 1 and
      day 2 or 3 of cycle 3; methotrexate intrathecally (IT) on day 2 of cycles 1 and 3; and
      cytarabine IT on day 8 of cycles 1 and 3. Patients may also receive rituximab IV on days 1
      and 8 of cycles 1 and 3. Cycles alternate every 3-4 weeks in the absence of disease
      progression or unacceptable toxicity.

      CYCLES 2, 4, 8, AND 10: Patients receive methotrexate IV over approximately 2 hours and then
      continuously over approximately 22 hours on day 1; cytarabine IV over approximately 3 hours
      BID on days 2-3; inotuzumab ozogamicin IV over approximately 1 hour on day 2 or 3 of cycles 2
      and 4; cytarabine IT on day 5 of cycles 2 and 4; and methotrexate IT on day 8 of cycles 2 and
      4. Patients may also receive rituximab IV on days 1 and 8 of cycles 2 and 4. Cycles alternate
      every 3-4 weeks in the absence of disease progression or unacceptable toxicity.

      CYCLES 5, 6, 11, AND 12: Patients receive blinatumomab as a continuous intravenous infusion
      (CIVI) on days 1-29. Treatment repeats every 42 days for 4 cycles in the absence of disease
      progression or unacceptable toxicity.

      MAINTENANCE THERAPY: Patients receive mercaptopurine orally (PO) BID and methotrexate PO once
      weekly for 3 years. Patients also receive vincristine sulfate IV over 30 minutes once monthly
      and prednisone PO daily five times a month for 1 year. Treatment continues in the absence of
      disease progression or unacceptable toxicity. Patients who did not receive blinatumomab
      during induction and consolidation can receive 4 consecutive cycles of blinatumomab as in
      cycles 5, 6, 11, and 12, at any time during maintenance, after discussion with the principal
      investigator and if in the best interest of the patient.

      TREATMENT OF MINIMAL RESIDUAL DISEASE (MRD): Patients with MRD may receive additional cycles
      of inotuzumab ozogamicin IV every 3-4 weeks for up to 6 doses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and every 4 months.