Thromb Haemost 2019; 119(05): 844-853
DOI: 10.1055/s-0039-1679938
Trial Protocol Design Paper
Georg Thieme Verlag KG Stuttgart · New York

PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)—Rationale and Design

Sarah H. O'Brien
1  Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital/The Ohio State University, Columbus, Ohio, United States
,
Danshi Li
2  Cardiovascular, Innovative Medicines Development, Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Lesley G. Mitchell
3  Division Pediatric Hematology/Oncology, University of Alberta, Edmonton, Alberta, Canada
,
Thomas Hess
2  Cardiovascular, Innovative Medicines Development, Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Pamela Zee
2  Cardiovascular, Innovative Medicines Development, Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Donald L. Yee
4  Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States
,
Jane W. Newburger
5  Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, United States
6  Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts, United States
,
Lillian Sung
7  Children's Oncology Group Cancer Control Chair, The Hospital for Sick Children, Toronto, Ontario, Canada
,
Vilmarie Rodriguez
8  Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States
› Author Affiliations
Funding This study is supported by Bristol Myers Squibb and Pfizer.
Further Information

Publication History

06 August 2018

10 January 2019

Publication Date:
12 March 2019 (eFirst)

Abstract

Venous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B cell lymphoblastic lymphoma (T/B cell LL) can result not only in life-threatening acute complications but also contribute to significant long-term sequelae. The PREVAPIX-ALL study is an open-label randomized controlled study comparing outcomes of treatment with prophylactic dose apixaban versus no anticoagulation (standard of care) in children and adolescents with ALL and T/B cell LL receiving standard induction chemotherapy with asparaginase and the presence of a central venous access device. On day 29 of induction, all patients undergo screening imaging with duplex ultrasonography and echocardiography. The primary efficacy endpoint of the study is a composite of symptomatic and asymptomatic VTE that includes deep vein thrombosis, pulmonary embolism, cerebral sinovenous thrombosis or VTE-related death. The primary safety outcome is major bleeding. Secondary outcomes are central line-associated infections, patency and line replacement, superficial thrombosis, arterial events and death. A planned sample size of 500 randomized paediatric patients enrolled over a period of 5 years is based on the estimation of VTE rates of 20 and 10% in the standard of care and apixaban groups, respectively. An optional biomarker study in 150 patients will examine predictors of increased VTE risk and study in vivo anticoagulant effects of apixaban in children by measuring specific biomarkers in the haemostatic system and inflammatory pathway. This study will provide valuable information for the safety and efficacy of apixaban in VTE prevention during induction in paediatric ALL.