A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT02723994
- Lead Sponsor
- Incyte Corporation
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 171
-
Eligible for study when participant is 1 year to 21 years at the time of diagnosis
-
Eligible Ages in 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ruxolitinib in combination with chemotherapy Dexamethasone - Ruxolitinib in combination with chemotherapy Leucovorin Calcium - Ruxolitinib in combination with chemotherapy Asparaginase Erwinia Chrysanthemi - Ruxolitinib in combination with chemotherapy Doxorubicin - Ruxolitinib in combination with chemotherapy Pegaspargase - Ruxolitinib in combination with chemotherapy Cytarabine - Ruxolitinib in combination with chemotherapy Ruxolitinib - Ruxolitinib in combination with chemotherapy Methotrexate - Ruxolitinib in combination with chemotherapy Thioguanine - Ruxolitinib in combination with chemotherapy Vincristine Sulfate - Ruxolitinib in combination with chemotherapy Mercaptopurine - Ruxolitinib in combination with chemotherapy Prednisone - Ruxolitinib in combination with chemotherapy Cyclophosphamide -
- Primary Outcome Measures
Name Time Method Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms Part 1: AEs assessed from screening through up to 30 days after the last dose of study drug, expected to be 26 months (females) or 38 months (males) 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 Part 2: assessed at 3 years
- Secondary Outcome Measures
Name Time Method Safety and tolerability of the combination treatment for subjects beginning treatment at the recommended dose for Part 2, as assessed by AEs, vital signs, clinical laboratory tests, and echocardiograms AEs assessed from screening through up to 30 days after the last dose of study treatment, expected to be 26 months (females) or 38 months (males)
Trial Locations
- Locations (108)
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Childrens Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Childrens Hospital
🇺🇸Houston, Texas, United States
Kaiser Permanente
🇺🇸San Diego, California, United States
Rady Children'S Hospital - San Diego
🇺🇸San Diego, California, United States
Children'S Hospitals and Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Texas Health Science Cente
🇺🇸San Antonio, Texas, United States
Loma Linda University Cancer Center
🇺🇸Loma Linda, California, United States
Miller Childrens Hospital Pharmacy
🇺🇸Long Beach, California, United States
Kaiser Foundation Health Plan
🇺🇸Los Angeles, California, United States
Southern California Permanente Medical Group
🇺🇸Los Angeles, California, United States
Valley Childrens Hospital
🇺🇸Madera, California, United States
Lucille Packard Childrens Hospital
🇺🇸Palo Alto, California, United States
Choc Children Hospital
🇺🇸Orange, California, United States
Kaiser Permanente Downey
🇺🇸Santa Fe Springs, California, United States
Connecticut Children'S Medical Ctr
🇺🇸Hartford, Connecticut, United States
Alfred I. Dupont Hospital For Children
🇺🇸Wilmington, Delaware, United States
Nemours Childrens Clinic
🇺🇸Pensacola, Florida, United States
Childrens Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Joe Dimaggio Children Hospital
🇺🇸Hollywood, Florida, United States
University of Florida Health Shands Hospital
🇺🇸Jacksonville, Florida, United States
All Childrens Hospital
🇺🇸Saint Petersburg, Florida, United States
Egleston Children'S Health
🇺🇸Atlanta, Georgia, United States
Saint Marys Medical Center
🇺🇸West Palm Beach, Florida, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Ann & Robert H. Lurie Children'S Hospital
🇺🇸Chicago, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Riley Hospital For Children
🇺🇸Indianapolis, Indiana, United States
St Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Dana Farber Boston Children'S
🇺🇸Boston, Massachusetts, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Helen Devos Childrens Hosp
🇺🇸Grand Rapids, Michigan, United States
Michigan State University
🇺🇸Lansing, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Alliance For Childhood Diseases
🇺🇸Las Vegas, Nevada, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Rutgers Cancer Institute of Nj
🇺🇸New Brunswick, New Jersey, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Cohen Children'S Medical Center
🇺🇸New Hyde Park, New York, United States
Nyu Clinical Cancer Center
🇺🇸New York, New York, United States
Suny Upstate Medical University
🇺🇸Syracuse, New York, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Akron Children'S Hospital
🇺🇸Akron, Ohio, United States
Rainbow Babies & Children Hosp
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
Children'S Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Hasbro Childrens Hospital
🇺🇸Providence, Rhode Island, United States
Driscoll Children'S Hospital
🇺🇸Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
El Paso Children'S Hospital Corporation
🇺🇸El Paso, Texas, United States
Children'S Hospital of the
🇺🇸Norfolk, Virginia, United States
Providence Sacred Heart Medical Center & Children'S Hospital
🇺🇸Spokane, Washington, United States
Seattle Children'S Hospital
🇺🇸Seattle, Washington, United States
Bc Children'S Hospital
🇨🇦Vancouver, British Columbia, Canada
McGill University Health Centre/Glen Site/Cedars Cancer Centre
🇨🇦Montreal, Quebec, Canada
McMaster University Medical Centre
🇨🇦Hamilton, Canada
University Pediatric Hospital
🇵🇷San Juan, Puerto Rico
Ucsf Pediatric Oncology
🇺🇸San Francisco, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Primary Children'S Hospital
🇺🇸Salt Lake City, Utah, United States
Nationwide Children'S Hospital
🇺🇸Columbus, Ohio, United States
Children'S Center For Cancer & Blood Dis
🇺🇸Las Vegas, Nevada, United States
Children'S Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Chu Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Arkansas Childrens Hospital
🇺🇸Little Rock, Arkansas, United States
St Josephs Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
San Jorge Childrens Hospital
🇵🇷San Juan, Puerto Rico
Alberta'S Children Hospital
🇨🇦Calgary, Alberta, Canada
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Albany Medical College
🇺🇸Albany, New York, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Maine Center For Cancer Medicine
🇺🇸Scarborough, Maine, United States
Phoenix Children'S Hospital
🇺🇸Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
The Childrens Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Children'S Hospital & Medical Center
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Doernbecher Childrens Hospital
🇺🇸Portland, Oregon, United States
The Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
St Josephs Childrens Hospital Tampa
🇺🇸Tampa, Florida, United States
Children'S Hospital Colorado
🇺🇸Aurora, Colorado, United States
New York Medical College
🇺🇸Valhalla, New York, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Cs Mott Childrens Hospital
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
Smilow Cancer Center - Yale
🇺🇸New Haven, Connecticut, United States
Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital For Children
🇺🇸Orlando, Florida, United States
Kosair Childrens Hospital
🇺🇸Louisville, Kentucky, United States
The Children'S Mercy Hospital Outpatient
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of North Carolina At Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Ochsner Clinic
🇺🇸New Orleans, Louisiana, United States
Kapiolani Medical Center For Women and Children
🇺🇸Honolulu, Hawaii, United States
Dell Childrens Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Blank Childrens Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Dayton Children'S Hospital
🇺🇸Dayton, Ohio, United States