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

Phase 3

Completed

Conditions: Lymphoma
Acute Lymphoblastic Leukemia

Interventions: Other: No systemic anticoagulant prophylaxis
Drug: Apixaban

Registration Number: NCT02369653

Lead Sponsor: Bristol-Myers Squibb

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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 512

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
No systemic anticoagulant prophylaxis	No systemic anticoagulant prophylaxis	No systemic anticoagulant prophylaxis
Apixaban	Apixaban	Children aged 1 to \<18 years weighing 6 to \<35 kg randomized to apixaban will receive a fixed dose apixaban based on body weight tier twice a day for approximately 28 days. Children aged 1 to \<18 years weighing ≥ 35 kg will receive 2.5 mg of apixaban twice a day for approximately 28 days. Subjects ≥ 5 years may be administered either 2.5-mg, 0.5-mg tablets or oral solution apixaban. Subjects \< 5years and \< 35 kg may be administered 0.5-mg tablets only

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death	From first dose up to approximately 40 days after first dose	The number of participants with non-fatal deep vein thromboses (DVT) (including asymptomatic and symptomatic), pulmonary embolism (PE), cerebral venous sinus thrombosis (CVST); and venous thromboembolism (VTE) related-death objectively confirmed by a blinded, independent adjudication committee. Symptomatic events are included during the intended treatment period. Asymptomatic events are included from scans up to Day 40.
The Number of Participants With Adjudicated Major Bleeding	From first dose up to approximately 34 days after first dose	The number of participants with major bleeding adjudicated by a blinded, independent adjudication committee. Adjudicated major bleeding is defined as bleeding that satisfies one or more of the following criteria: 1. fatal bleeding 2. clinically overt bleeding associated with a decrease in hemoglobin of at least 20g/L (ie, 2g/dL) in a 24-hour period 3. bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS; and/or 4. bleeding that requires surgical intervention in an operating suite, including interventional radiology.

Secondary Outcome Measures

Name	Time	Method
The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)	From first dose up to approximately 40 days after first dose	The number of participants with non-fatal asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)	From first dose up to approximately 34 days after first dose	The number of participants with non-fatal symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
The Number of Participants With Non-fatal Pulmonary Embolism (PE)	From first dose up to approximately 34 days after first dose	The number of participants with non-fatal pulmonary embolism (PE) adjudicated by a blinded, independent adjudication committee
The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)	From first dose up to approximately 34 days after first dose	The number of participants with cerebral venous sinus thrombosis (CVST) adjudicated by a blinded, independent adjudication committee
The Number of Participants With Venous Thromboembolism (VTE)-Related-death	From first dose up to approximately 34 days after first dose	The number of participants with venous thromboembolism (VTE)-related-death adjudicated by a blinded, independent adjudication committee
The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)	From first dose up to approximately 34 days after first dose	The number of participants with major and clinically relevant non-major bleeding (CRNMB) adjudicated by a blinded, independent adjudication committee CRNM bleeding is defined as bleeding that satisfies one or both of the following: 1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and 2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
The Number of Participant Deaths	From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)	The number of participant deaths adjudicated by a blinded, independent adjudication committee
The Number of Participants With an Arterial Thromboembolic Event	From first dose up to approximately 34 days after first dose	The number of participants with an arterial thromboembolic event including paradoxical embolism and stroke adjudicated by a blinded, independent adjudication committee
The Number of Participants With a CVAD-Related Infection	From first dose up to approximately 34 days after first dose	The number of participants with a central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee
The Number of Participants Needing Catheter Replacements During the Study	From first dose up to approximately 34 days after first dose	The number of participants needing catheter replacements during the study
The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use	From first dose up to approximately 34 days after first dose	The number of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use
The Number Participants Experiencing Superficial Vein Thrombosis Events	From first dose up to approximately 34 days after first dose	The number participants experiencing superficial vein thrombosis events. Clots that occur in a superficial vein ie, cephalic vein, basilic vein (upper extremity) or saphenous vein (lower extremity) confirmed by radiographic imaging.
The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)	From first dose up to approximately 34 days after first dose	The number of participants with clinically relevant non-major bleeding events (CRNMB) adjudicated by a blinded, independent adjudication committee. CRNM bleeding is defined as bleeding that satisfies one or both of the following: 1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and 2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
The Number of Participants With Minor Bleeding Events	From first dose up to approximately 34 days after first dose	The number of participants with minor bleeding events adjudicated by a blinded, independent adjudication committee. Minor bleeding defined as any overt or macroscopic evidence of bleeding that does not fulfill the criteria for either major bleeding or CRNMB
The Number of Platelet Transfusions Needed During the Study	From first dose up to approximately 34 days after first dose	The number of platelet transfusions needed during the study. The events are not adjudicated. A subject could have more than one platelet transfusion.
Maximum Observed Concentration (Cmax)	pre-dose, 1-4 hours post dose	The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Trough Observed Concentration (Cmin)	pre-dose, 1-4 hours post dose	The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Area Under the Concentration-Time Curve [AUC(TAU)]	pre-dose, 1-4 hours post dose	The area under the concentration-time curve \[AUC(TAU)\] was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Anti-FXa Activity	pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.	Anti-FXa Activity was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy

Trial Locations

Locations (73): Sinai Hospital Of Baltimore
🇺🇸
Baltimore, Maryland, United States
University Hospitals
🇺🇸
Cleveland, Ohio, United States
Children'S Center For Cancer And Blood Diseases
🇺🇸
Indianapolis, Indiana, United States
Cincinnati Children'S Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Children's Hospital of San Antonio
🇺🇸
San Antonio, Texas, United States
University Hospital
🇺🇸
San Antonio, Texas, United States
University Of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Children'S Hospital Of Orange County
🇺🇸
Orange, California, United States
Phoenix Children'S Hospital/Ctr. For Cancer & Blood Ctr.
🇺🇸
Phoenix, Arizona, United States
Children's Hospital at TriStar Centennial
🇺🇸
Nashville, Tennessee, United States
Monroe Carell Jr Children'S Hosp. At Vanderbilt Tower
🇺🇸
Nashville, Tennessee, United States
All Childrens Hospital Specialty Physicians
🇺🇸
Saint Petersburg, Florida, United States
University Of Louisville
🇺🇸
Louisville, Kentucky, United States
Nemours Children'S Clinic
🇺🇸
Jacksonville, Florida, United States
Childrens Hospital Of La
🇺🇸
Los Angeles, California, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Childrens Healthcare Of Atlanta - E
🇺🇸
Atlanta, Georgia, United States
Shands Hospital At University Of Florida
🇺🇸
Gainesville, Florida, United States
Ochsner Medical Center
🇺🇸
New Orleans, Louisiana, United States
City of Hope
🇺🇸
Duarte, California, United States
St. Luke'S Mountain State Tumor Institute
🇺🇸
Boise, Idaho, United States
Childrens Hospital New Orleans
🇺🇸
New Orleans, Louisiana, United States
University Of Michigan Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
Navicent Health Physician Group
🇺🇸
Macon, Georgia, United States
University Of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Driscoll Children'S Hospital
🇺🇸
Corpus Christi, Texas, United States
Children'S Hospital London Health Sciences Centre
🇨🇦
London, Ontario, Canada
SUNY Upstate Medical University
🇺🇸
Syracuse, New York, United States
Penn State Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Klinika Transplantacji Szpiku Onkologii i Hematologii Dzieciecej
🇵🇱
Wroclaw, Poland
Oddzial Hematologii i Onkologii Dzieciecej
🇵🇱
Zabrze, Poland
Klinika detske onkologie
🇨🇿
Brno, Czechia
Unv. Of Nc At Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Children'S Hospital Of Eastern Ontario
🇨🇦
Ottawa, Ontario, Canada
Nationwide Children'S Hospital
🇺🇸
Columbus, Ohio, United States
Children's Hospital Of Pittsburgh Of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Local Institution
🇷🇺
St.petersburg, Russian Federation
Monash Medical Centre Clayton
🇦🇺
Clayton, Victoria, Australia
Texas Children's Cancer and Hematology Centers
🇺🇸
Houston, Texas, United States
Queensland Children's Hospital
🇦🇺
Sth Brisbane, Queensland, Australia
Mayo Clinic Rochester
🇺🇸
Rochester, Minnesota, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Golisano Childrens Hospital of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
Loma Linda University Cancer Center
🇺🇸
Loma Linda, California, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Yale University School Of Medicine
🇺🇸
New Haven, Connecticut, United States
Nemours / A. I. duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Nemours Children'S Clinic - Orlando
🇺🇸
Orlando, Florida, United States
Nemours Children'S Clinic-Pensacola
🇺🇸
Pensacola, Florida, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Valerie Fund Children's Center at St. Joseph's Children's Hospital
🇺🇸
Paterson, New Jersey, United States
Wake Forest Baptist Health
🇺🇸
Winston-Salem, North Carolina, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Scott & White - McLane Children's Specialty Clinic
🇺🇸
Temple, Texas, United States
MultiCare Institute for Research & Innovation
🇺🇸
Tacoma, Washington, United States
Alberta Children'S Hospital
🇨🇦
Calgary, Alberta, Canada
St. Marys Medical Center
🇺🇸
West Palm Beach, Florida, United States
Akron Children'S Hospital
🇺🇸
Akron, Ohio, United States
Rady Children'S Hospital - San Diego
🇺🇸
San Diego, California, United States
University Of Rochester General Clinical Research Center
🇺🇸
Rochester, New York, United States
Blank Childrens Hospital
🇺🇸
Des Moines, Iowa, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Dell Children'S Medical Center Of Central Texas
🇺🇸
Austin, Texas, United States
Childrens Hospitals And Clinics Of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Childrens Hospital Of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Providence Sacred Heart Medical Center
🇺🇸
Spokane, Washington, United States
Lucile Packard Children's Hospital (LPCH)
🇺🇸
Palo Alto, California, United States