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

Why are we doing this research?

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.

DETAILED DESCRIPTION:

PRIMARY OUTCOME MEASURES:

  • Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms
  • Part 2: Efficacy of ruxolitinib in combination with chemotherapy as measured by Event-free survival, defined as the percentage of patients alive without relapse, progression, or death at 3 years from study Day 1

Study Type: Interventional

Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY: 1 Year to 21 Years

ELIGIBILITY 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 ≥ 3 × 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

Conditions

  • Leukemia ALL New Diagnosis
  • Adult - Leukemia ALL New Diagnosis

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave.
Cincinnati OH 45229-3039

Phone: 513-636-2799
cancer@cchmc.org