Summary

for people ages 1-21 (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Mignon Loh, MD

Description

Summary

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.

Official Title

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

Keywords

Leukemia B-cell acute lymphoblastic leukemia (ALL) pediatric multi-agent chemotherapy JAK inhibitor Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Cytarabine Dexamethasone Prednisone Cyclophosphamide Doxorubicin Methotrexate Vincristine Asparaginase Mercaptopurine Pegaspargase Thioguanine Ruxolitinib Asparaginase Erwinia Chrysanthemi Leucovorin Calcium Vincristine Sulfate

Eligibility

You can join if…

Open to people ages 1-21

  • 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 × 103/μL

  • CNS3 leukemia at diagnosis
  • Systemic steroid pretreatment without presteroid WBC documentation
  • Diagnostic bone marrow or peripheral blood sample must have gene expression profiling and downstream genetic testing performed by submitting diagnostic specimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study. Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested by low density microarray testing at the COG ALL reference laboratory or TriCore laboratory at the University of New Mexico AND must contain 1 of the following genetic lesions: (determined at COG ALL reference laboratories, or equivalent

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*† as determined by a COG ALL Reference Laboratory
  4. 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 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

You CAN'T join if...

  • 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 m2

  • 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 × 103/μL

  • Absolute neutrophil count (ANC) < 750/μL
  • Positive screen for hepatitis B or C
  • Known human immunodeficiency virus infection

Locations

  • UCSF Pediatric Hematology/Oncology accepting new patients
    San Francisco California 94143 United States
  • Valley Children's Hospital accepting new patients
    Madera California 93636 United States

Lead Scientist

  • Mignon Loh, MD
    Professor, Pediatrics. Authored (or co-authored) 54 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Incyte Corporation
ID
NCT02723994
Phase
Phase 2
Study Type
Interventional
Last Updated