NCT02369653

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)

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
512

participants targeted

Target at P75+ for phase_3 lymphoma

Timeline
Completed

Started Oct 2015

Geographic Reach
12 countries

96 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

February 24, 2015

Completed
8 months until next milestone

Study Start

First participant enrolled

October 22, 2015

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 7, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 7, 2021

Completed
8 months until next milestone

Results Posted

Study results publicly available

March 8, 2022

Completed
Last Updated

March 8, 2022

Status Verified

February 1, 2022

Enrollment Period

5.7 years

First QC Date

January 21, 2015

Results QC Date

January 7, 2022

Last Update Submit

February 10, 2022

Conditions

Keywords

Anticoagulation

Outcome Measures

Primary Outcomes (2)

  • The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death

    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.

    From first dose up to approximately 40 days after first dose

  • The Number of Participants With Adjudicated Major Bleeding

    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.

    From first dose up to approximately 34 days after first dose

Secondary Outcomes (19)

  • 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 Symptomatic Deep Vein Thromboses (DVT)

    From first dose up to approximately 34 days after first dose

  • 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 Cerebral Venous Sinus Thrombosis (CVST)

    From first dose up to approximately 34 days after first dose

  • The Number of Participants With Venous Thromboembolism (VTE)-Related-death

    From first dose up to approximately 34 days after first dose

  • +14 more secondary outcomes

Study Arms (2)

Apixaban

EXPERIMENTAL

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

Drug: Apixaban

No systemic anticoagulant prophylaxis

PLACEBO COMPARATOR

No systemic anticoagulant prophylaxis

Other: No systemic anticoagulant prophylaxis

Interventions

Apixaban
No systemic anticoagulant prophylaxis

Eligibility Criteria

Age1 Year - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (96)

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

Phoenix, Arizona, 85016, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Loma Linda University Cancer Center

Loma Linda, California, 92350, United States

Location

Childrens Hospital Of La

Los Angeles, California, 90027, United States

Location

Children'S Hospital Of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children's Hospital (LPCH)

Palo Alto, California, 94304, United States

Location

Rady Children'S Hospital - San Diego

San Diego, California, 92123-4282, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Nemours / A. I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Golisano Childrens Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

Shands Hospital At University Of Florida

Gainesville, Florida, 32610-0298, United States

Location

Nemours Children'S Clinic

Jacksonville, Florida, 32207, United States

Location

Nemours Children'S Clinic - Orlando

Orlando, Florida, 32827, United States

Location

Nemours Children'S Clinic-Pensacola

Pensacola, Florida, 32504, United States

Location

All Childrens Hospital Specialty Physicians

St. Petersburg, Florida, 33701, United States

Location

St. Marys Medical Center

West Palm Beach, Florida, 33407, United States

Location

Childrens Healthcare Of Atlanta - E

Atlanta, Georgia, 30342, United States

Location

Navicent Health Physician Group

Macon, Georgia, 31201, United States

Location

St. Luke'S Mountain State Tumor Institute

Boise, Idaho, 83712, United States

Location

Children'S Center For Cancer And Blood Diseases

Indianapolis, Indiana, 46260, United States

Location

Blank Childrens Hospital

Des Moines, Iowa, 50309, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0293, United States

Location

University Of Louisville

Louisville, Kentucky, 40202, United States

Location

Childrens Hospital New Orleans

New Orleans, Louisiana, 70118, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Sinai Hospital Of Baltimore

Baltimore, Maryland, 21215, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University Of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Childrens Hospitals And Clinics Of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

University Of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

University Of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

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

Paterson, New Jersey, 07503, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University Of Rochester General Clinical Research Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Unv. Of Nc At Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Akron Children'S Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children'S Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

Nationwide Children'S Hospital

Columbus, Ohio, 43205, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18017, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital Of Pittsburgh Of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

Location

Monroe Carell Jr Children'S Hosp. At Vanderbilt Tower

Nashville, Tennessee, 37232, United States

Location

Dell Children'S Medical Center Of Central Texas

Austin, Texas, 78723, United States

Location

Driscoll Children'S Hospital

Corpus Christi, Texas, 78411, United States

Location

Texas Children's Cancer and Hematology Centers

Houston, Texas, 77030, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

University Hospital

San Antonio, Texas, 78284, United States

Location

Scott & White - McLane Children's Specialty Clinic

Temple, Texas, 76502, United States

Location

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

MultiCare Institute for Research & Innovation

Tacoma, Washington, 98405, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution

New Lambton Heights, New South Wales, 2305, Australia

Location

Queensland Children's Hospital

Sth Brisbane, Queensland, 4101, Australia

Location

Monash Medical Centre Clayton

Clayton, Victoria, 3168, Australia

Location

Local Institution

Parkville, Victoria, 3052, Australia

Location

Local Institution

Brussels, 1020, Belgium

Location

Local Institution

Brussels, 1200, Belgium

Location

Local Institution

Edegem, 2650, Belgium

Location

Local Institution

Ghent, 9000, Belgium

Location

Local Institution

Leuven, 3000, Belgium

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Local Institution

Edmonton, Alberta, T6G 2B7, Canada

Location

Local Institution

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Children'S Hospital London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children'S Hospital Of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Klinika detske onkologie

Brno, 613 00, Czechia

Location

Local Institution

Budapest, 1094, Hungary

Location

Local Institution

Debrecen, 4032, Hungary

Location

Local Institution

Pécs, 7623, Hungary

Location

Local Institution

Guadalajara, Jalisco, 44340, Mexico

Location

Local Institution

Df, Mexico City, 04530, Mexico

Location

Local Institution

Monterrey, Nuevo León, 64460, Mexico

Location

Local Institution

Christchurch, 8011, New Zealand

Location

Klinika Transplantacji Szpiku Onkologii i Hematologii Dzieciecej

Wroclaw, 50-556, Poland

Location

Oddzial Hematologii i Onkologii Dzieciecej

Zabrze, 41-800, Poland

Location

Local Institution

Caguas, 00725, Puerto Rico

Location

Local Institution

Kirov, 610027, Russia

Location

Local Institution

Moscow, 115478, Russia

Location

Local Institution

Moscow, 117198, Russia

Location

Local Institution

Saint Petersburg, 197341, Russia

Location

Local Institution

Saint Petersburg, 197758, Russia

Location

Local Institution

Seoul, 03080, South Korea

Location

Local Institution

Seoul, 03722, South Korea

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

LymphomaPrecursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

apixaban

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, LymphoidLeukemiaHematologic Diseases

Results Point of Contact

Title
Bristol-Myers Squibb Study Director
Organization
Bristol-Myers Squibb

Study Officials

  • Bristol-Myers Squibb

    Bristol-Myers Squibb

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2015

First Posted

February 24, 2015

Study Start

October 22, 2015

Primary Completion

July 7, 2021

Study Completion

July 7, 2021

Last Updated

March 8, 2022

Results First Posted

March 8, 2022

Record last verified: 2022-02

Locations