A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia

Inclusion Criteria:

• Eligible for study when participant is 1 year to 21 years at the time of diagnosis

• Eligible Ages in Canada; 2 years to 21 years

• De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are presentat diagnosis:

• Age ≥ 10 years

• White blood cell (WBC) ≥ 50 × 10^3/μL

• CNS3 leukemia at diagnosis

• Systemic steroid pretreatment without presteroid WBC documentation

• Diagnostic bone marrow or peripheral blood sample must have gene expressionprofiling and downstream genetic testing performed by submitting diagnosticspecimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or itssuccessor study. Specimens must demonstrate a Ph-like expression profile (ie,LDA-positive) as tested by low density microarray testing at the COG ALL referencelaboratory or TriCore laboratory at the University of New Mexico AND must contain 1of the following genetic lesions: (determined at COG ALL reference laboratories, orequivalent CAP/CLIA-certified laboratories approved by the medical monitor:

1. CRLF2 rearrangement with confirmed JAK1 or JAK2 mutation (JAK+)

2. CRLF2 rearrangement without JAK mutation

3. Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions,IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status asdetermined by a COG ALL Reference Laboratory

• Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent)in Study AALL1131 or its successor study, or as per the institutional standard ofcare for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed

• Male and female subjects of reproductive non childbearing potential or willing totake appropriate precautions to avoid pregnancy or fathering a child for theduration of study participation

Exclusion Criteria:

• Receipt of any other cytotoxic chemotherapy before Induction therapy, with exceptionof hydroxyurea or steroid pretreatment

• Trisomy 21 (Down syndrome)

• BCR-ABL1-rearranged (Ph+) ALL

• Calculated creatinine clearance or radioisotope glomerular filtration rate < 70mL/min/1.73 m^2

• Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age

• Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)

• History or evidence of cirrhosis

• Platelet count < 75 × 10^3/μL

• Absolute neutrophil count (ANC) < 750/μL

• Positive screen for hepatitis B or C

• Known human immunodeficiency virus infection