Clinical trial NCT02723994: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Leukemia
Keywords: B-cell acute lymphoblastic leukemia (ALL)
pediatric
multi-agent chemotherapy
JAK inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Children's Oncology Group
First posted: 2016-03-31
Enrollment: 171
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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:

  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
* 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

Primary outcomes:
measure: Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms
timeFrame: 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)
measure: 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
timeFrame: Part 2: assessed at 3 years
Secondary outcomes:
measure: 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
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Childrens Hospital of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children'S Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Childrens Hospital
state: Arkansas
city: Fontana
country: United States
facility: Kaiser Permanente
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Long Beach
country: United States
facility: Miller Childrens Hospital Pharmacy
state: California
city: Los Angeles
country: United States
facility: Children'S Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Kaiser Foundation Health Plan
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Madera
country: United States
facility: Valley Childrens Hospital
state: California
city: Orange
country: United States
facility: Choc Children Hospital
state: California
city: Palo Alto
country: United States
facility: Lucille Packard Childrens Hospital
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: San Diego
country: United States
facility: Rady Children'S Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: Ucsf Pediatric Oncology
state: California
city: Santa Fe Springs
country: United States
facility: Kaiser Permanente Downey
state: California
city: Aurora
country: United States
facility: Children'S Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children'S Medical Ctr
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Center - Yale
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I. Dupont Hospital For Children
state: Delaware
city: Fort Myers
country: United States
facility: Childrens Hospital of Southwest Florida
state: Florida
city: Hollywood
country: United States
facility: Joe Dimaggio Children Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital For Children
state: Florida
city: Pensacola
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Saint Petersburg
country: United States
facility: All Childrens Hospital
state: Florida
city: Tampa
country: United States
facility: St Josephs Childrens Hospital Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Marys Medical Center
state: Florida
city: Atlanta
country: United States
facility: Egleston Children'S Health
state: Georgia
city: Honolulu
country: United States
facility: Kapiolani Medical Center For Women and Children
state: Hawaii
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children'S Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Indianapolis
country: United States
facility: St Vincent Hospital
state: Indiana
city: Des Moines
country: United States
facility: Blank Childrens Hospital
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Childrens Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Scarborough
country: United States
facility: Maine Center For Cancer Medicine
state: Maine
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber Boston Children'S
state: Massachusetts
city: Ann Arbor
country: United States
facility: Cs Mott Childrens Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Helen Devos Childrens Hosp
state: Michigan
city: Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Minneapolis
country: United States
facility: Children'S Hospitals and Clinics of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: The Children'S Mercy Hospital Outpatient
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Children'S Hospital & Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Alliance For Childhood Diseases
state: Nevada
city: Las Vegas
country: United States
facility: Children'S Center For Cancer & Blood Dis
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of Nj
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Paterson
country: United States
facility: St Josephs Regional Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children'S Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Nyu Clinical Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: Suny Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina At Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Akron
country: United States
facility: Akron Children'S Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies & Children Hosp
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children'S Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children'S Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Portland
country: United States
facility: Doernbecher Childrens Hospital
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children'S Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Childrens Hospital of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Childrens Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Dell Childrens Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children'S Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: El Paso
country: United States
facility: El Paso Children'S Hospital Corporation
state: Texas
city: Houston
country: United States
facility: Texas Childrens Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Cente
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children'S Hospital
state: Utah
city: Norfolk
country: United States
facility: Children'S Hospital of the
state: Virginia
city: Seattle
country: United States
facility: Seattle Children'S Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center & Children'S Hospital
state: Washington
city: Green Bay
country: United States
facility: St Vincent Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta'S Children Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Bc Children'S Hospital
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital For Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Chu Sainte-Justine
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre/Glen Site/Cedars Cancer Centre
state: Quebec
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
city: San Juan
country: Puerto Rico
facility: San Jorge Childrens Hospital
city: San Juan
country: Puerto Rico
facility: University Pediatric Hospital
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, MD
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Philadelphia, Philadelphia, PA
name: Sarah Tasian, MD
role: STUDY_CHAIR
References: