Protocol No.: OCR15238
Sponsor Protocol No.: AALL1521; INCB 18424-269
Protocol Title.: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
Principal Investigator: Slayton, William
Objective: 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.
Phase: Phase II
Age Group: Both
Age: 1 Year - 21 Years
Treatment: In Part 1, ruxolitinib will be administered at a protocol-defined starting dose in combination with chemotherapy, with dose escalation and de-escalation following the rolling 6 study design. The established recommended starting dose will be taken forward into Part 2.
Detailed Eligibility: INCLUSION CRITERIA: 1. Ages 1 to 21 years of age 2. 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 3. 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 4. 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 5. 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: 1. Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment 2. Trisomy 21 (Down syndrome) 3. BCR-ABL1-rearranged (Ph+) ALL 4. Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/min/1.73 m^2 5. Alanine aminotransferase ≥ 3 × upper limit of normal (ULN) for age 6. Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN) 7. History or evidence of cirrhosis 8. Platelet count < 75 × 10^3/μL 9. Absolute neutrophil count (ANC) < 750/μL 10. Positive screen for hepatitis B or C 11. Known human immunodeficiency virus infection