Inclusion Criteria

• Patients must have B-ALL with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
• Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a phycoerythrin [PE] fluorophore is strongly recommended)
• In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
• Patient must have one of the following:
• Second or greater relapse
• Primary refractory disease with at least 2 prior induction attempts
• First or greater relapse refractory to at least one prior re-induction attempt
• Relapsed patients previously diagnosed with B-lymphoblastic lymphoma are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
• Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to = grade 2 or lower per the inclusion/exclusion criteria prior to entering this study

Exclusion Criteria

• Patients with any prior history of SOS/VOD irrespective of severity
• Patients with isolated central nervous system (CNS), testicular, or other extramedullary site of relapse
• Patients who have been previously treated with InO
• Patients with active optic nerve and/or retinal involvement that would require urgent radiation therapy concurrent with protocol therapy; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy and intrathecal chemotherapy)
• Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD medications (meds)
• Patients who are currently receiving or plan to receive corticosteroids except as described below
• Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, as a premedication for InO and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study