TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial

Irene L M Klaassen, Mandy N Lauw, Marianne D van de Wetering, Bart J Biemond, Saskia Middeldorp, Floor C H Abbink, Marc Bierings, D Maroeska M W Te Loo, Rob Pieters, Inge M van der Sluis, Wim J E Tissing, C Michel Zwaan, C Heleen van Ommen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase.

METHODS/DESIGN: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75% with a power of 80%, using a two-sided test with significance level α = 0.05.

DISCUSSION: This trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design.

TRAIL REGISTRATION: Nederlands Trial Register NTR4707 . Registered 30 July 2014.

Original languageEnglish
Pages (from-to)122
JournalBMC Pediatrics
Volume17
Issue number1
DOIs
Publication statusPublished - 10 May 2017

Cite this

Klaassen, Irene L M ; Lauw, Mandy N ; van de Wetering, Marianne D ; Biemond, Bart J ; Middeldorp, Saskia ; Abbink, Floor C H ; Bierings, Marc ; Te Loo, D Maroeska M W ; Pieters, Rob ; van der Sluis, Inge M ; Tissing, Wim J E ; Michel Zwaan, C ; Heleen van Ommen, C. / TropicALL study : Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial. In: BMC Pediatrics. 2017 ; Vol. 17, No. 1. pp. 122.
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abstract = "BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase.METHODS/DESIGN: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75{\%} with a power of 80{\%}, using a two-sided test with significance level α = 0.05.DISCUSSION: This trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design.TRAIL REGISTRATION: Nederlands Trial Register NTR4707 . Registered 30 July 2014.",
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Klaassen, ILM, Lauw, MN, van de Wetering, MD, Biemond, BJ, Middeldorp, S, Abbink, FCH, Bierings, M, Te Loo, DMMW, Pieters, R, van der Sluis, IM, Tissing, WJE, Michel Zwaan, C & Heleen van Ommen, C 2017, 'TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial' BMC Pediatrics, vol. 17, no. 1, pp. 122. https://doi.org/10.1186/s12887-017-0877-x

TropicALL study : Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial. / Klaassen, Irene L M; Lauw, Mandy N; van de Wetering, Marianne D; Biemond, Bart J; Middeldorp, Saskia; Abbink, Floor C H; Bierings, Marc; Te Loo, D Maroeska M W; Pieters, Rob; van der Sluis, Inge M; Tissing, Wim J E; Michel Zwaan, C; Heleen van Ommen, C.

In: BMC Pediatrics, Vol. 17, No. 1, 10.05.2017, p. 122.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - TropicALL study

T2 - Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial

AU - Klaassen, Irene L M

AU - Lauw, Mandy N

AU - van de Wetering, Marianne D

AU - Biemond, Bart J

AU - Middeldorp, Saskia

AU - Abbink, Floor C H

AU - Bierings, Marc

AU - Te Loo, D Maroeska M W

AU - Pieters, Rob

AU - van der Sluis, Inge M

AU - Tissing, Wim J E

AU - Michel Zwaan, C

AU - Heleen van Ommen, C

PY - 2017/5/10

Y1 - 2017/5/10

N2 - BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase.METHODS/DESIGN: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75% with a power of 80%, using a two-sided test with significance level α = 0.05.DISCUSSION: This trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design.TRAIL REGISTRATION: Nederlands Trial Register NTR4707 . Registered 30 July 2014.

AB - BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase.METHODS/DESIGN: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75% with a power of 80%, using a two-sided test with significance level α = 0.05.DISCUSSION: This trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design.TRAIL REGISTRATION: Nederlands Trial Register NTR4707 . Registered 30 July 2014.

KW - Adolescent

KW - Anticoagulants

KW - Antineoplastic Agents

KW - Asparaginase

KW - Child

KW - Child, Preschool

KW - Clinical Protocols

KW - Drug Administration Schedule

KW - Female

KW - Follow-Up Studies

KW - Heparin, Low-Molecular-Weight

KW - Humans

KW - Infant

KW - Male

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Prospective Studies

KW - Treatment Outcome

KW - Venous Thromboembolism

KW - Young Adult

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

U2 - 10.1186/s12887-017-0877-x

DO - 10.1186/s12887-017-0877-x

M3 - Article

VL - 17

SP - 122

JO - BMC Pediatrics

JF - BMC Pediatrics

SN - 1471-2431

IS - 1

ER -