Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

Inclusion Criteria:

Age

• Participants must be < 22 years of age.

Diagnosis

• Participants must have B-ALL with persistent or rising MRD between 0.1 and 4.99%without extramedullary disease following at least two prior induction attempts,relapse or after hematopoietic stem cell transplant

• Leukemia blasts demonstrating surface expression of CD22

Performance Level

• Karnofsky or Lansky performance score ≥ 50% (corresponding to ECOG Score of ≥ 2).The Lansky performance score should be used for participants < 16 years and theKarnofsky performance score for participants ≥ 16 years.

Prior Therapy

• Patients must have fully recovered from the acute toxic effects of all prioranticancer therapy, defined as resolution of all such toxicities to ≤ Grade 2 orlower per the inclusion/exclusion criteria prior to entering this study.

• At least 14 days must have elapsed since the completion of cytotoxic therapy, withthe exception of standard maintenance therapy and steroids.

• At least 7 days must have elapsed since completion of therapy with a biologic agent.For agents that have known adverse events occurring beyond 7 days afteradministration, this period prior to enrollment must be extended beyond the timeduring which adverse events are known to occur.

• At least 3 half-lives must have elapsed since prior therapy that included amonoclonal antibody with the exception of blinatumomab. Patients must have been offblinatumomab infusion for at least 7 days and all drug related toxicity must haveresolved to Grade 2 or lower as outlined in the inclusion/exclusion criteria.

• At least 42 days must have elapsed since CAR-T cell therapy.

• Participant has received ≤ 1 prior bone marrow transplant.

• At least 90 days have elapsed since bone marrow transplant and participant is offimmune suppression for ≥ 2 weeks, if applicable with no evidence of active GVHD.

• At least 2 weeks must have elapsed since local XRT (small port); ≥ 3 months musthave elapsed if prior cranial or craniospinal XRT was received, if ≥ 50% of thepelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if othersubstantial bone marrow irradiation was given.

Organ Function Requirements

• Adequate renal function defined as glomerular filtration rate ≥ 60 cc/min/1.73m2 orserum creatinine based on age as follows:

• Age: <6 months; maximum serum creatinine (mg/dL): 0.4 (male, female); Age: 6months to <1 year; maximum serum creatinine (mg/dL): 0.5 (male, female); Age: 1to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female); Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female); Age: 6 to <10years; maximum serum creatinine (mg/ dL): 1 (male, female); Age: 10 to <13years; maximum serum creatinine (mg/dL): 1.2 (male, female); Age: 13 to <16years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female); Age: ≥ 16years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)

• Adequate hepatic function defined as:

• Direct bilirubin ≤ 1.4 mg/dL (if total bilirubin > 1.4 mg/dL) and

• AST or ALT ≤ 3 x ULN for age.

• Adequate cardiac function defined as shortening fraction of ≥ 27% or ejectionfraction ≥ 45%.

Exclusion Criteria:

• History of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of anyseverity.

• Concurrent chemotherapy or targeted anti-cancer agents, other than intrathecaltherapy.

• Patient with concurrent severe and/or uncontrolled medical conditions that, in theopinion of the investigator, may impair participation in the study or the evaluationof safety and/or efficacy.

• Known HIV infection or active hepatitis B (defined as hepatitis B surfaceantigen-positive) or C (defined as hepatitis C antibody-positive).

• Pregnant or lactating (female participant of childbearing potential must havenegative serum or urine pregnancy test required within 7 days prior to start oftreatment).

• Male or female participant of reproductive potential must agree to use appropriatemethods of contraception for the duration of study treatment and for at least 30days after last dose of protocol treatment.

• Inability or unwillingness of research participant or legal guardian/representativeto give written informed consent.