This study aims to improve outcomes for patients with NCI High Risk B-Cell Acute Lymphoblastic Leukemia (B-ALL) and patients with NCI Standard Risk B-ALL with high risk features. High risk features are when the leukemia has spread to the spinal fluid or testes, or one received steroid treatment before being diagnosed with leukemia.
   
This study is being done in multiple parts. Part 1 will help determine participants risk group after Consolidation therapy. Samples will be tested and reviewed by experts to confirm the type of leukemia each participant has. Samples for this study will also determine if certain characteristics in the leukemia cells indicate whether or not someone will have a good response to therapy, and if they might benefit from other types of therapy than the one offered in this clinical trial.

The treatment in Part 1 of this study takes about 3 months: 5 weeks for Induction therapy and 8 weeks for Consolidation therapy. The treatment involves medicine called chemotherapy, which fights cancer. The treatment in this study is standard-of-care therapy for people with high risk B-ALL and standard risk B-ALL with high-risk features. All medications in this part of the study are approved by the U.S. Food and Drug Administration (FDA).

If participants continue to part 2 of the study, there are three possible treatment plans they could be assigned to.

HR-Fav B-ALL: Participants will all receive standard-of-care treatment for patients with HR-Fav B-ALL. Standard of care treatment and tests have been defined by prior clinical trials and are currently used for patients who are not participating in research studies. HR-Fav patients will not be eligible to receive the investigational medicine on this study.
   
HR B-ALL: Participants will be randomized to one of two treatment arms.

• HR Arm A: Participants will receive standard-of-care treatment for patients with high risk B-ALL
• HR Arm B: Participants will receive standard-of-care treatment plus 2 cycles of the investigational medicine, Inotuzumab Ozogamicin (InO). InO has been approved by the FDA for use in treating relapsed and refractory B-ALL in adults, but has not yet been approved in children. It is given to patients intravenously.