Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia

Inclusion Criteria:

• Patients must be >= 1 year and < 22 years of age at the time of enrollment

• Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL),with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease

• NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollmenton this study

• Patients with ALL or B-LL who have M2 morphology must have local confirmatorytesting showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method

• Leukemic blasts must demonstrate surface expression of CD22 at the time of relapseby local/institutional flow cytometry of a bone marrow aspirate sample; (assessmentof CD22 using a bright fluorophore such as phycoerythrin [PE] is stronglyrecommended)

• In the case of an inadequate aspirate sample (dry tap) or if bone marrowaspirate is unable to be performed due to patient clinical status, flowcytometry of peripheral blood specimen may be substituted if the patient has atleast 1,000/uL circulating blasts; alternatively, CD22 expression may bedocumented by immunohistochemistry of a bone marrow biopsy specimen

• Patients with one of the following:

• Second or greater relapse;

• Primary refractory disease with at least 2 prior induction attempts;

• First relapse refractory to at least one prior re-induction attempt

• Any relapse after HSCT (Cohort 1 ONLY)

Patients with Down syndrome are eligible ONLY for Cohort 1 with:

• Any of above disease status, OR

• First relapse with no prior re-induction attempt NOTE: Patients with Down syndromeor prior HSCT are NOT eligible for Cohort 2 combination therapy

• Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapyattempts including two different tyrosine kinase inhibitors (TKIs)

• Patients must have fully recovered from the acute toxic effects of all prioranti-cancer therapy, defined as resolution of all such toxicities to =< grade 2or lower per the inclusion/exclusion criteria prior to entering this study.Apply to Cohort 2:

• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. Foragents not listed, the duration of this interval must be discussed with the studychair and the study-assigned Research Coordinator prior to enrollment.

• A waiting period prior to enrollment is not required for patients receivingstandard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).

• A waiting period is not required for patients receiving a single dose ofintrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days priorto enrollment

• >= 14 days must have elapsed after the completion of other cytotoxic therapy,with the exception of hydroxyurea, for patients not receiving standardmaintenance therapy. For patients who previously received calaspargase pegol, >= 21 days must have elapsed after the last dose. Additionally, patients musthave fully recovered from all acute toxic effects of prior therapy.

• Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hoursprior to the start of protocol therapy.

• Anti-cancer agents not known to be myelosuppressive (e.g., not associated withreduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after thelast dose of agent. For agents not listed, the duration of this interval must bediscussed with the study chair and the study-assigned research coordinator prior toenrollment.

• Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusionof last dose of antibody, and toxicity related to prior antibody therapy must berecovered to grade =< 1. There is an exception for blinatumomab infusions, for whichpatients must have been off for at least 3 days and all drug related toxicity musthave resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.

• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting periodprior to enrollment is not required for patients receiving corticosteroid forleukemia therapy/cytoreduction.

• Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinalXRT was received, if >= 50% of the pelvis was irradiated, or if total bodyirradiation (TBI) was received; >= 6 weeks must have elapsed if other substantialbone marrow irradiation was given.

• Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must haveelapsed since stem cell transplant and at least 30 days from donor lymphocyteinfusion. Patient must have had no more than one previous HSCT and currently have noevidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT isallowed.

• Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsedfrom the last CAR-T cell infusion

• Patients must have a performance status corresponding to Eastern CooperativeOncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16years of age and Lansky for patients =< 16 years of age; patients who areunable to walk because of paralysis, but who are up in a wheelchair, will beconsidered ambulatory for the purpose of assessing the performance score

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or

• A serum creatinine based on age/gender as follows:

• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)

• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)

• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)

• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)

• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)

• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)

• Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L

Exclusion Criteria:

• Patients with any prior history of SOS irrespective of severity

• Patients with isolated central nervous system (CNS), testicular, or any otherextramedullary site of relapse

• Patients who have been previously treated with inotuzumab ozogamicin

• Patients who have previously received HSCT (Cohort 2 only)

• Patients with Down syndrome (Cohort 2 only)

• History of allergic reaction attributed to compounds of similar or biologiccomposition to inotuzumab ozogamicin or other agents in the study

• Note: Patients with history of allergy to pegaspargase/calaspargase pegol areeligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase canbe obtained

• Patients with active optic nerve and/or retinal involvement are not eligible;patients who are presenting with visual disturbances should have an ophthalmologicexam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve orretinal 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 ofprotocol therapy, and intrathecal chemotherapy)

• Anti-GVHD or agents to prevent organ rejection post-transplant; patients who arereceiving cyclosporine, tacrolimus, or other agents to prevent eithergraft-versus-host disease post bone marrow transplant or organ rejectionpost-transplant are not eligible for this trial; at least 3 half-lives must haveelapsed after the last dose of GVHD or anti-rejection medications

• Patients who are currently receiving or plan to receive corticosteroids except asdescribed below

• Systemic corticosteroids may be administered for cytoreduction up to 24 hoursprior to the start of protocol therapy, (Cohort 1 only) for all patients,corticosteroids may be administered as a premedication for inotuzumabozogamicin and as treatment for allergic reactions or for physiologicreplacement/stress dosing of hydrocortisone for documented adrenalinsufficiency; corticosteroids are not allowed for other indications

• Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections;testing to prove negative status is not required for enrollment unless it is deemednecessary for usual medical care of the patient

• Patients who have an active uncontrolled infection defined as:

• Positive bacterial blood culture within 48 hours of study enrollment;

• Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment withclinical signs of infection; fever that is determined to be due to tumor burdenis allowed if patients have documented negative blood cultures for at least 48hours prior to enrollment and no concurrent signs or symptoms of activeinfection or hemodynamic instability

• A positive fungal culture within 30 days of study enrollment or active therapyfor presumed invasive fungal infection

• Patients may be receiving IV or oral antibiotics to complete a course oftherapy for a prior documented infection as long as cultures have been negativefor at least 48 hours and signs or symptoms of active infection have resolved;for patients with clostridium (C.) difficile diarrhea, at least 72 hours ofantibacterial therapy must have elapsed and stools must have normalized tobaseline

• Active viral or protozoal infection requiring IV treatment

• Patients known to have one of the following concomitant genetic syndromes: Bloomsyndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failuresyndrome

• There have been no human studies of inotuzumab ozogamicin in pregnant women and noreports of exposure in utero; based on nonclinical safety studies, inotuzumabozogamicin has the potential to impair human male and female fertility and toadversely affect human embryo fetal development; women of childbearing potentialshould be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin;there is no information regarding the presence of inotuzumab ozogamicin in humanmilk, the effects on the breast-fed infant, or the effects on milk production;because of the potential for adverse reactions in breast-fed infants, women shouldnot breast-feed during treatment with inotuzumab ozogamicin and for at least 2months after the final dose

• Female patients of childbearing potential are not eligible unless a negativepregnancy test result has been obtained within 7 days prior to enrollment

• Female patients who are sexually active and of reproductive potential are noteligible unless they agree to use an effective contraceptive method for theduration of their study participation and for 8 months after the last dose ofinotuzumab ozogamicin

• Men with female partners of childbearing potential should use effectivecontraception during treatment with inotuzumab ozogamicin and for at least 5months after the last dose of inotuzumab ozogamicin

• Lactating females are not eligible unless they agree not to breastfeed theirinfants