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

NCT ID: NCT02369653

Last Updated: 2022-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 512 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-22
• Study Completion Date: 2021-07-07

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)

Conditions

Lymphoma; Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

No systemic anticoagulant prophylaxis

No systemic anticoagulant prophylaxis

Group Type: PLACEBO_COMPARATOR

No systemic anticoagulant prophylaxis

Intervention Type: OTHER

Interventions

Apixaban

Intervention Type: DRUG

No systemic anticoagulant prophylaxis

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Phoenix Children'S Hospital/Ctr. For Cancer & Blood Ctr.

Phoenix, Arizona, United States

City of Hope

Duarte, California, United States

Loma Linda University Cancer Center

Loma Linda, California, United States

Childrens Hospital Of La

Los Angeles, California, United States

Children'S Hospital Of Orange County

Orange, California, United States

Lucile Packard Children's Hospital (LPCH)

Palo Alto, California, United States

Rady Children'S Hospital - San Diego

San Diego, 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

Golisano Childrens Hospital of Southwest Florida

Fort Myers, Florida, United States

Shands Hospital At University Of Florida

Gainesville, Florida, United States

Nemours Children'S Clinic

Jacksonville, Florida, United States

Nemours Children'S Clinic - Orlando

Orlando, Florida, United States

Nemours Children'S Clinic-Pensacola

Pensacola, Florida, United States

All Childrens Hospital Specialty Physicians

St. Petersburg, Florida, United States

St. Marys Medical Center

West Palm Beach, Florida, United States

Childrens Healthcare Of Atlanta - E

Atlanta, Georgia, United States

Navicent Health Physician Group

Macon, Georgia, United States

St. Luke'S Mountain State Tumor Institute

Boise, Idaho, United States

Children'S Center For Cancer And Blood Diseases

Indianapolis, Indiana, United States

Blank Childrens Hospital

Des Moines, Iowa, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kentucky

Lexington, Kentucky, United States

University Of Louisville

Louisville, Kentucky, United States

Childrens Hospital New Orleans

New Orleans, Louisiana, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

Sinai Hospital Of Baltimore

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

University Of Michigan Cancer Center

Ann Arbor, Michigan, United States

Childrens Hospitals And Clinics Of Minnesota

Minneapolis, Minnesota, United States

University Of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

University Of Mississippi Medical Center

Jackson, Mississippi, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Valerie Fund Children's Center at St. Joseph's Children's Hospital

Paterson, New Jersey, United States

Albany Medical Center

Albany, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

University Of Rochester General Clinical Research Center

Rochester, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

New York Medical College

Valhalla, New York, United States

Unv. Of Nc At Chapel Hill

Chapel Hill, North Carolina, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Akron Children'S Hospital

Akron, Ohio, United States

Cincinnati Children'S Hospital Medical Center

Cincinnati, Ohio, United States

University Hospitals

Cleveland, Ohio, United States

Nationwide Children'S Hospital

Columbus, Ohio, United States

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital Of Pittsburgh Of UPMC

Pittsburgh, Pennsylvania, 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

Dell Children'S Medical Center Of Central Texas

Austin, Texas, United States

Driscoll Children'S Hospital

Corpus Christi, Texas, United States

Texas Children's Cancer and Hematology Centers

Houston, Texas, United States

Children's Hospital of San Antonio

San Antonio, Texas, United States

University Hospital

San Antonio, Texas, United States

Scott & White - McLane Children's Specialty Clinic

Temple, Texas, United States

Providence Sacred Heart Medical Center

Spokane, Washington, United States

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Local Institution

New Lambton Heights, New South Wales, Australia

Queensland Children's Hospital

Sth Brisbane, Queensland, Australia

Monash Medical Centre Clayton

Clayton, Victoria, Australia

Local Institution

Parkville, Victoria, Australia

Local Institution

Brussels, , Belgium

Local Institution

Brussels, , Belgium

Local Institution

Edegem, , Belgium

Local Institution

Ghent, , Belgium

Local Institution

Leuven, , Belgium

Alberta Children'S Hospital

Calgary, Alberta, Canada

Local Institution

Edmonton, Alberta, Canada

Local Institution

St. John's, Newfoundland and Labrador, Canada

Children'S Hospital London Health Sciences Centre

London, Ontario, Canada

Children'S Hospital Of Eastern Ontario

Ottawa, Ontario, Canada

Klinika detske onkologie

Brno, , Czechia

Local Institution

Budapest, , Hungary

Local Institution

Debrecen, , Hungary

Local Institution

Pécs, , Hungary

Local Institution

Guadalajara, Jalisco, Mexico

Local Institution

Df, Mexico City, Mexico

Local Institution

Monterrey, Nuevo León, Mexico

Local Institution

Christchurch, , New Zealand

Klinika Transplantacji Szpiku Onkologii i Hematologii Dzieciecej

Wroclaw, , Poland

Oddzial Hematologii i Onkologii Dzieciecej

Zabrze, , Poland

Local Institution

Caguas, , Puerto Rico

Local Institution

Kirov, , Russia

Local Institution

Moscow, , Russia

Local Institution

Moscow, , Russia

Local Institution

Saint Petersburg, , Russia

Local Institution

Saint Petersburg, , Russia

Local Institution

Seoul, , South Korea

Local Institution

Seoul, , South Korea

Countries

United States; Australia; Belgium; Canada; Czechia; Hungary; Mexico; New Zealand; Poland; Puerto Rico; Russia; South Korea

References

Rodriguez V, O'Brien SH, Orgel E, Schultz CL, Esbenshade AJ, Memaj A, Dyme JL, Favatella NA, Mitchell LG. Safety and efficacy of apixaban thrombosis prevention in pediatric patients with obesity and acute lymphoblastic leukemia. Blood Adv. 2025 Sep 23;9(18):4738-4747. doi: 10.1182/bloodadvances.2025016160.

Reference Type: DERIVED

PMID: 40505060 (View on PubMed)

O'Brien SH, Rodriguez V, Lew G, Newburger JW, Schultz CL, Orgel E, Derr K, Ranalli MA, Esbenshade AJ, Hochberg J, Kang HJ, Dinikina Y, Mills D, Donovan M, Dyme JL, Favatella NA, Mitchell LG; PREVAPIX-ALL investigators. Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024 Jan;11(1):e27-e37. doi: 10.1016/S2352-3026(23)00314-9. Epub 2023 Nov 16.

Reference Type: DERIVED

PMID: 37980924 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Investigator Inquiry Form

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

2014-000328-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CV185-155

Identifier Type: -

Identifier Source: org_study_id