A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
Leukemia
About this trial
This is an interventional treatment trial for Leukemia focused on measuring B-cell acute lymphoblastic leukemia (ALL), pediatric, multi-agent chemotherapy, JAK inhibitor
Eligibility Criteria
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 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:
- CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)
- CRLF2 rearrangement* without JAK mutation
- 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
- 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
- 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
Sites / Locations
- The Childrens Hospital of Alabama
- Phoenix Children'S Hospital
- Arkansas Childrens Hospital
- Kaiser Permanente
- Loma Linda University Cancer Center
- Miller Childrens Hospital Pharmacy
- Children'S Hospital Los Angeles
- Kaiser Foundation Health Plan
- Southern California Permanente Medical Group
- Valley Childrens Hospital
- Choc Children Hospital
- Lucille Packard Childrens Hospital
- Kaiser Permanente
- Rady Children'S Hospital - San Diego
- Ucsf Pediatric Oncology
- Kaiser Permanente Downey
- Children'S Hospital Colorado
- Connecticut Children'S Medical Ctr
- Smilow Cancer Center - Yale
- Alfred I. Dupont Hospital For Children
- Childrens Hospital of Southwest Florida
- Joe Dimaggio Children Hospital
- Nemours Childrens Clinic
- University of Florida Health Shands Hospital
- Florida Hospital Orlando
- Arnold Palmer Hospital For Children
- Nemours Childrens Clinic
- All Childrens Hospital
- St Josephs Childrens Hospital Tampa
- Saint Marys Medical Center
- Egleston Children'S Health
- Kapiolani Medical Center For Women and Children
- Ann & Robert H. Lurie Children'S Hospital
- Loyola University Medical Center
- Southern Illinois University School of Medicine
- Riley Hospital For Children
- St Vincent Hospital
- Blank Childrens Hospital
- University of Iowa Hospital and Clinics
- University of Kentucky
- Kosair Childrens Hospital
- Ochsner Clinic
- Maine Center For Cancer Medicine
- Sinai Hospital of Baltimore
- Johns Hopkins University
- Dana Farber Boston Children'S
- Cs Mott Childrens Hospital
- Helen Devos Childrens Hosp
- Michigan State University
- University of Minnesota
- Children'S Hospitals and Clinics of Minnesota
- University of Mississippi Medical Center
- The Children'S Mercy Hospital Outpatient
- Washington University
- Children'S Hospital & Medical Center
- Alliance For Childhood Diseases
- Children'S Center For Cancer & Blood Dis
- Hackensack University Medical Center
- Morristown Medical Center
- Rutgers Cancer Institute of Nj
- Newark Beth Israel Medical Center
- St Josephs Regional Medical Center
- University of New Mexico Hospital
- Albany Medical College
- Roswell Park Comprehensive Cancer Center
- Cohen Children'S Medical Center
- Weill Cornell Medical College
- Nyu Clinical Cancer Center
- University of Rochester Medical Center
- Suny Upstate Medical University
- New York Medical College
- University of North Carolina At Chapel Hill
- Carolinas Medical Center
- Wake Forest University
- Akron Children'S Hospital
- Cincinnati Childrens Hospital Medical Center
- Rainbow Babies & Children Hosp
- Cleveland Clinic Foundation
- Nationwide Children'S Hospital
- Dayton Children'S Hospital
- Toledo Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Hospital and Health Center
- Doernbecher Childrens Hospital
- Penn State Hershey Medical Center
- Children'S Hospital of Philadelphia
- Childrens Hospital of Pittsburgh
- Hasbro Childrens Hospital
- Medical University of South Carolina
- Vanderbilt University Medical Center
- Dell Childrens Medical Center of Central Texas
- Driscoll Children'S Hospital
- Medical City Dallas Hospital
- University of Texas Southwestern Medical Center
- El Paso Children'S Hospital Corporation
- Texas Childrens Hospital
- University of Texas Health Science Cente
- Primary Children'S Hospital
- Children'S Hospital of the
- Seattle Children'S Hospital
- Providence Sacred Heart Medical Center & Children'S Hospital
- St Vincent Hospital
- Medical College of Wisconsin
- Alberta'S Children Hospital
- Bc Children'S Hospital
- The Hospital For Sick Children
- Chu Sainte-Justine
- McGill University Health Centre/Glen Site/Cedars Cancer Centre
- McMaster University Medical Centre
- San Jorge Childrens Hospital
- University Pediatric Hospital
Arms of the Study
Arm 1
Experimental
Ruxolitinib in combination with chemotherapy