Comparing Inotuzumab Combined With Low Intensity Chemotherapy Plus Blinatumomab to Usual Chemotherapy Plus Blinatumomab in Older Adults With CD22+ B-cell Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVE: I. To compare measurable residual disease (MRD) negative event-free survival (EFS) rate of the experimental arm (A) to standard arm (B) with EFS defined as time from randomization to occurrence of an event. SECONDARY OBJECTIVES: I. To determine overall response rate (complete response \[CR\] + complete remission with partial hematologic recovery \[CRh\] + complete remission with incomplete platelet counts \[CRp\] + complete remission with incomplete blood count recovery \[CRi\]) at designated time points (after cycle 1, after cycle 2, end of blinatumomab \[blina\]-1, end of intensive phase/blina-4) in each treatment arm. II. To determine rate of flow cytometry MRD-negativity (undetectable or detectable \< 10\^-4) at designated time points (after cycle 1, after cycle 2, end of blina-1, end of intensive phase/blina-4) in each treatment arm. III. To compare MRD response by central aspirate multiparameter flow cytometry (Wood lab) Children's Hospital of Los Angeles \[CHLA\]) to next generation sequencing MRD assessment (clonoSEQ, Adaptive) of blood and bone marrow at designated time points (after cycle 1, after cycle 2, and end of blina-1) and to determine association with outcome, (EFS, disease free survival \[DFS\], overall survival \[OS\]) in each treatment arm. IV. To determine the event-free survival (EFS) standard-definition (event defined as failure to achieve morphologic remission by end of cycle 2, hematologic relapse, death), disease-free survival (DFS), overall survival (OS) of each arm (median, 6-month, 1-year, 2-year, 3-year) in each treatment arm. V. To determine proportion of patients who proceed to allogeneic transplant after initial response (without intervening salvage therapy) in each treatment arm. VI. To determine rate of liver toxicity (grade 3-5 alanine aminotransferase \[ALT\] increase, aspartate aminotransferase \[AST\] increase, bilirubin increase, alkaline phosphatase increase). VII. To describe the safety and tolerability of each arm including rate of grade 3-5 non-hematologic toxicity and treatment-related mortality (grade 5 toxicity VIII. To determine rate of delays in intensive-phase chemotherapy due to neutropenia and thrombocytopenia (in responding patients). IX. To assess the baseline variations in comorbidity burden, physical, nutritional, and cognitive function of the study participants, and explore the association between comorbidity burden, physical, nutritional, and cognitive function, and the outcomes of therapy (grade 3-5 non-hematological toxicities, and OS). X. To explore the longitudinal changes in physical, nutritional, and cognitive function among the experimental and control groups. XI. To compare the burden of patient-reported symptomatic adverse events between treatment arms using the Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). XII. To correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters. XIII. To correlate specific karyotype groups with response rates, response duration, MRD, and survival in patients treated on this study. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: INDUCTION/CONSOLIDATION: \*CHEMOTHERAPY (CHEMO) CYCLE 1: Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on days 2 and 8, cyclophosphamide IV over 3 hours every 12 hours (Q12H) on days 1-3, vincristine IV on days 1 and 8, dexamethasone IV or orally (PO) on days 1-4 and 11-14. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. Patients receive methotrexate intrathecally (IT) on day 2 and cytarabine IT on day 8. CHEMO CYCLE 2: Patients will receive inotuzumab ozogamicin IV over 1 hour on days 2 and 8, methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. Patients also receive cytarabine IT on day 2 and methotrexate IT on day 8. * BLINA-1 \& BLINA-2: Patients receive blinatumomab IV continuously on days 1-28. Patients also receive alternating cytarabine IT and methotrexate IT on days 2 and 8. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. At the end of Cycle 2, patients \< 70 years of age proceed to BLINA-3 \& BLINA-4 treatment. * CHEMO CYCLE 3: Patients receive inotuzumab ozogamicin IV over 1 hour on days 2 and 8, cyclophosphamide IV over 3 hours Q12H on days 1-3, vincristine IV on days 1 and 8, and dexamethasone IV or PO on days 1-4 and 11-14. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. * CHEMO CYCLE 4: Patients receive inotuzumab ozogamicin IV over 1 hour on days 2 and 8, methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. * BLINA-3 \& BLINA-4: Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive vincristine IV on day 1, prednisone PO daily on days 1-5, mercaptopurine PO twice daily (BID) on days 1-28, and methotrexate PO weekly. Treatment repeats every 28 days for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study. ARM B: INDUCTION/CONSOLIDATION: * CHEMO CYCLE 1: Patients receive cyclophosphamide IV over 3 hours Q12H on days 1-3, doxorubicin IV over 24 hours on day 4, vincristine IV on days 1 and 8, dexamethasone IV or PO on days 1-4 and 11-14. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. Patients receive methotrexate IT on day 2 and cytarabine IT on day 8. * CHEMO CYCLE 2: Patients receive methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8. Patients also receive cytarabine IT on day 2 and methotrexate IT on day 8. * BLINA-1 \& BLINA-2: Patients receive blinatumomab IV continuously on days 1-28. Patients also receive alternating cytarabine IT and methotrexate IT on days 2 and 8. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. At the end of Cycle 2 patients \< 70 years of age, proceed to BLINA-3 \& BLINA-4 treatment. * CHEMO CYCLE 3: Patients receive cyclophosphamide IV over 3 hours Q12H on days 1-3, doxorubicin IV over 24 hours on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or PO on days 1-4 and 11-14. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. * CHEMO CYCLE 4: Patients receive methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing \>= 20% CD20 also receive rituximab IV on days 2 and 8. * BLINA-3 \& BLINA-4: Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive vincristine IV on day 1, prednisone PO daily on days 1-5, mercaptopurine PO BID on days 1-28, and methotrexate PO weekly. Treatment repeats every 28 days for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 2 months until 1 year after completion of therapy, every 3 months until 2 years after completion of therapy, and then every 6 months until 5 years from study registration.