Phase 2 Study of Ruxolitinib W/Chemo in Children With ALL

INCB 18424-269 (AALL1521) - A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia

  • Clinical Trial Information

    Trial Contact: Leffin, Melissa; El-Shami, Jessica; Spinelli, Jennifer

  • IRB No: 17.045.04

    Protocol Abbrev: INCB 18424-269

    Principal Investigator: Vincent F. Giusti, MD

    Phase: Drug: Phase II

    Age Group: Pediatric

    Secondary Protocol No: INCB 18424-269 (AALL1521)

    Treatment: Ruxolitinib

    Therapies Involved: Chemotherapy

    ClinicalTrials.gov ID: NCT02723994

  • Objective

    Part 1
    •   To evaluate initial safety and tolerability and to define the recommended Part 2 dose (RP2D) of ruxolitinib in combination with multi-agent chemotherapy in children and adolescents or young adults (AYA) with de novo high-risk (HR) Philadelphia chromosome–like (Ph-like) cytokine receptor–like factor 2 rearranged (CRLF2-R) and/or Janus kinase (JAK) pathway–mutant B-cell acute lymphoblastic leukemia (B-ALL).
    Part 2
    •   To determine the efficacy of ruxolitinib in combination with chemotherapy for children and AYA with de novo HR Ph-like CRLF2-R and/or JAK pathway–mutant B-ALL.

  • Key Eligibility

    Ages Eligible for Study: 1 Year to 21 Years (Child, Adult)
    Sexes Eligible for Study: All
    Accepts Healthy Volunteers: No

    Criteria


    Inclusion Criteria:

    •  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


    •  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