Clinical trial NCT02369653: A Study of the Safety and Effectiveness of Apixaban in Preventing Blood Clots in Children With Leukemia Who Have a Central Venous Catheter and Are Treated With Asparaginase
Official title: A Phase III Randomized, Open Label, Multi-center Study of the Safety and Efficacy of Apixaban for Thromboembolism Prevention Versus No Systemic Anticoagulant Prophylaxis During Induction Chemotherapy in Children With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoma (T or B Cell) Treated With Asparaginase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Acute Lymphoblastic Leukemia
Keywords: Anticoagulation
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2015-02-24
Enrollment: 512
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare the effect of a blood thinning drug called Apixaban versus no administration of a blood thinning drug, in preventing blood clots in children with leukemia or lymphoma. Patients must be receiving chemotherapy, including asparaginase, and have a central line (a catheter inserted for administration of medications and blood sampling)


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* New diagnosis of de novo ALL, lymphomas (T or B cell), or mixed-phenotype acute leukemia
* Planned 3-4 drug systemic induction chemotherapy with a corticosteroid, vincristine and a single dose or multiple doses of asparaginase, with or without daunorubicin
* Functioning Central Venous Access Device
* Must be able to tolerate oral medication or have it administered via an Nasogastric tube (NGT) or GT tube
* Males and females,age 1 year(365 days) to \< 18 (17 years and 364 days) years.

Exclusion Criteria:

* Subjects scheduled to have \> 3 Lumbar Punctures over the course of the study treatment period
* Prior history of documented DVT or PE in the past 3 months
* Known inherited bleeding disorder or coagulopathy
* Major surgery \[excluding Central Venous Access Device (CVAD) replacement and bone marrow aspiration and non-open biopsy\] within the last 7 days prior to enrollment that may be associated with a risk of bleeding. Open biopsy is considered a major surgery.
* Uncontrolled severe hypertension at enrollment. Severe hypertension is defined as a systolic or diastolic blood pressure (BP) \> 5 mm Hg above the 95th percentile as defined by the National High Blood Pressure Education Program Working Group (NHBPEP) established guidelines for the definition of normal and elevated blood pressure in children
* Extreme hyperleukocytosis, white blood cell (WBC) counts over 200 x 109/L (200,000/microL) at the time of enrollment
* Liver dysfunction manifested by SGTP (ALT) \> 5X Upper limit of normal (ULN) and/or Aspartate aminotransferase (AST) \>5 X ULN and/or direct (conjugated) bilirubin \> 2X ULN
* Renal function \< 30% of normal for age and size as determined by the Schwartz formula
* International normalized ratio (INR) \> 1.4 and activated partial thromboplastin time (aPTT) \> 3 seconds above the upper limit of normal for age, within 1 week prior to enrollment.
* History of allergy to apixaban or Factor Xa inhibitors
* History of significant adverse reaction or major bleeding related adverse reaction to other anticoagulant or antiplatelet agents
* History of any significant drug allergy (such as anaphylaxis or hepatotoxicity
* Any investigational drug being administered during the study

Other protocol inclusion/exclusion criteria may apply

Primary outcomes:
measure: The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death
timeFrame: From first dose up to approximately 40 days after first dose
measure: The Number of Participants With Adjudicated Major Bleeding
timeFrame: From first dose up to approximately 34 days after first dose
Secondary outcomes:
measure: The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)
timeFrame: From first dose up to approximately 40 days after first dose
measure: The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With Non-fatal Pulmonary Embolism (PE)
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With Venous Thromboembolism (VTE)-Related-death
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participant Deaths
timeFrame: From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)
measure: The Number of Participants With an Arterial Thromboembolic Event
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With a CVAD-Related Infection
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants Needing Catheter Replacements During the Study
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number Participants Experiencing Superficial Vein Thrombosis Events
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Participants With Minor Bleeding Events
timeFrame: From first dose up to approximately 34 days after first dose
measure: The Number of Platelet Transfusions Needed During the Study
timeFrame: From first dose up to approximately 34 days after first dose
measure: Maximum Observed Concentration (Cmax)
timeFrame: pre-dose, 1-4 hours post dose
measure: Trough Observed Concentration (Cmin)
timeFrame: pre-dose, 1-4 hours post dose
measure: Area Under the Concentration-Time Curve [AUC(TAU)]
timeFrame: pre-dose, 1-4 hours post dose
measure: Anti-FXa Activity
timeFrame: pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children'S Hospital/Ctr. For Cancer & Blood Ctr.
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Of La
state: California
city: Orange
country: United States
facility: Children'S Hospital Of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital (LPCH)
state: California
city: San Diego
country: United States
facility: Rady Children'S Hospital - San Diego
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Wilmington
country: United States
facility: Nemours / A. I. duPont Hospital for Children
state: Delaware
city: Fort Myers
country: United States
facility: Golisano Childrens Hospital of Southwest Florida
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital At University Of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children'S Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children'S Clinic - Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children'S Clinic-Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Childrens Hospital Specialty Physicians
state: Florida
city: West Palm Beach
country: United States
facility: St. Marys Medical Center
state: Florida
city: Atlanta
country: United States
facility: Childrens Healthcare Of Atlanta - E
state: Georgia
city: Macon
country: United States
facility: Navicent Health Physician Group
state: Georgia
city: Boise
country: United States
facility: St. Luke'S Mountain State Tumor Institute
state: Idaho
city: Indianapolis
country: United States
facility: Children'S Center For Cancer And Blood Diseases
state: Indiana
city: Des Moines
country: United States
facility: Blank Childrens Hospital
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University Of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Childrens Hospital New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Sinai Hospital Of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University Of Michigan Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Childrens Hospitals And Clinics Of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Jackson
country: United States
facility: University Of Mississippi Medical Center
state: Mississippi
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Paterson
country: United States
facility: Valerie Fund Children's Center at St. Joseph's Children's Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: University Of Rochester General Clinical Research 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: Unv. Of Nc At Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Akron
country: United States
facility: Akron Children'S Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children'S Hospital
state: Ohio
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Childrens Hospital Of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital Of Pittsburgh Of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Children's Hospital at TriStar Centennial
state: Tennessee
city: Nashville
country: United States
facility: Monroe Carell Jr Children'S Hosp. At Vanderbilt Tower
state: Tennessee
city: Austin
country: United States
facility: Dell Children'S Medical Center Of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children'S Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer and Hematology Centers
state: Texas
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio
state: Texas
city: San Antonio
country: United States
facility: University Hospital
state: Texas
city: Temple
country: United States
facility: Scott & White - McLane Children's Specialty Clinic
state: Texas
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: New Lambton Heights
country: Australia
facility: Local Institution
state: New South Wales
city: Sth Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton
state: Victoria
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Bruxelles
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Gent
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Calgary
country: Canada
facility: Alberta Children'S Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: St, John's
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: London
country: Canada
facility: Children'S Hospital London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children'S Hospital Of Eastern Ontario
state: Ontario
city: Brno
country: Czechia
facility: Klinika detske onkologie
city: Budapest
country: Hungary
facility: Local Institution
city: Debrecen
country: Hungary
facility: Local Institution
city: Pecs
country: Hungary
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Christchurch
country: New Zealand
facility: Local Institution
city: Wroclaw
country: Poland
facility: Klinika Transplantacji Szpiku Onkologii i Hematologii Dzieciecej
city: Zabrze
country: Poland
facility: Oddzial Hematologii i Onkologii Dzieciecej
city: Caguas
country: Puerto Rico
facility: Local Institution
city: Kirov
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: St.petersburg
country: Russian Federation
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: