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

This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.

Inclusion Criteria

• Eligible for study when participant is 1 year to 21 years at the time of diagnosis
• Eligible Ages in Australia and Canada; 2 years to 21 years
• De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:
• Age ≥ 10 years
• White blood cell (WBC) ≥ 50 × 10^3/μL
• CNS3 leukemia
• Systemic steroid pretreatment without presteroid WBC documentation
• One of the following Ph-like ALL genetic lesions must be present in the diagnostic bone marrow or peripheral blood sample:
• CRLF2 rearrangement with JAK1 or JAK2 mutation (JAK+)
• CRLF2 rearrangement without JAK mutation
• Other JAK pathway alterations (eg, JAK2 fusions, erythropoietin receptor (EPO-R) fusions, SH2B3 deletions, interleukin-7 receptor-alpha (IL7RA) mutations) with or without CRLF2 rearrangement
• Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or as the institutional standard of care 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 to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation

Exclusion Criteria

• Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
• Trisomy 21 (Down syndrome)
• BCR-ABL1-rearranged (Ph+) ALL
• Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/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

Lead Organization
Incyte Corporation