Tests two antibody therapies in newly diagnosed children with lymphoblastic leukemia

Who can take part

• Enrollment on INITIALL
• Age 1-18.99 years at the time of enrollment on INITIALL
• B-Acute lymphoblastic leukemia or lymphoblastic lymphoma
• No prior chemotherapy excluding therapy given on or allowed by INITIALL
• NCI high-risk (age 10 years or greater or presenting WBC count ≥50,000 cells/microL) or NCI standard-risk and a HR clinical feature as listed below:; CNS3 disease (≥5 WBC/microL CSF with blasts present); Testicular involvement of leukemia; Steroid pretreatment defined as >24 hours of therapy in the 14 days prior to enrollment on INITIALL if a preceding WBC to define NCI risk is unavailable
• For lymphoblastic lymphoma, Stage 3-4 disease OR Stage 1-2 disease in patient ages ≥10 years OR HR clinical feature as defined above
• Adequate liver function defined as:; Total bilirubin ≤ 1.5x the upper limit of normal for age and alanine transaminase (ALT) ≤ 5x the upper limit of normal for age. Patients with an elevated total bilirubin due to hemolysis are eligible if they have a direct bilirubin <1.5x the upper limit of normal
• Adequate renal function defined as:; Calculated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m\^2 using the Bedside Schwartz equation OR creatinine below or equal to the maximum defined below:; Age: 1 to <2 years; maximum serum creatinine (mg/dL): 0.6 (male and female); Age: 2 to <6 years; maximum serum creatinine (mg/dL): 0.8 (male and female); Age: 6 to <10 years; maximum serum creatinine (mg/dL): 1.0 (male and female); Age: 10 to <13 years; maximum serum creatinine (mg/dL): 1.2 (male and female); Age: 13 to <16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female); Age: ≥16 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
• Eligibility for inclusion post-induction requires meeting the first 4 Inclusion criteria above AND:; Treatment on SJALL23H for Induction OR; Lymphoblastic lymphoma, initially treated on an SJALL protocol OR standard (non-protocol) therapy, without a complete response at the end of induction OR; NCI-SR ALL at diagnosis and treated with an SJALL protocol OR standard (non-protocol) therapy who have; Slow response to therapy (≥0.1% MRD at end of induction for patients with hyperdiploid ALL or ≥0.01% MRD at end of induction for others with ALL) OR; HR genetics as defined in the protocol; These patients may receive no more than 2 weeks of post-induction therapy and should be transitioned to SJALL23H post-induction as soon as the qualifying genetic or MRD result is available

Who cannot take part

• Presence of ETV6::RUNX1 fusion unless also having a HR clinical feature OR slow response to induction therapy
• For patients of reproductive potential, unwillingness to use effective contraception for the duration of protocol therapy
• History or presence of clinically relevant central nervous system (CNS) pathology or event such as epilepsy, childhood or adult non-febrile seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. History of simple febrile seizure during childhood and presence of CNS leukemia at diagnosis are not exclusions to participation
• Active uncontrolled infection
• Current active autoimmune disease or history of autoimmune disease with the potential for CNS involvement
• History of venoocclusive disease/ sinusoidal obstructive syndrome
• Unstable cardiac disease including QTc >500msec
• Inability or unwillingness to give informed consent/ assent as applicable
• Pregnant or lactating