TropicALL study

Not applicable

Primary objective:

To assess the efficacy of thromboprophylaxis with high prophylactic dose LMWH as compared with standard care without systemic thromboprophylaxis in children treated for primary ALL.

Secondary objectives:

1. To assess the safety of thromboprophylaxis using high prophylactic dose LMWH as compared with standard of care without systemic thromboprophylaxis in children treated for newly diagnosed ALL, by assessment of the incidence of the composite of major bleeding or clinically relevant non-major bleeding

2. To assess whether ALL treatment with thromboprophylaxis using high prophylactic dose LMWH as compared with standard of care without systemic thromboprophylaxis influences complete remission and (overall or disease-free) survival rates of childhood ALL

3. To identify clinical risk factors or hematological biomarkers in ALL patients with and without symptomatic objectified VTE; to increase insight in the pathogenesis of coagulation disorders during ALL treatment and to establish a risk model for VTE.

Eligibility for the TropicALL study will be evaluated directly after study inclusion in the ALL-11 or 12 study. In ALL-11, inclusion in the TropicALL study will take place within the first week of ALL treatment (day 11 at the latest), and after receiving written informed consent. Randomization will take place on day 11, the day before the first PEG-asparaginase administration (day 12). Randomization of each patient will be performed by a GCP proof randomization computer program at the DCOG trial office.



Non-continuous asparaginase schedule

Induction

- start: day 12 of Induction IA;

• continued until: day 54 (in total 43 days)
in Induction IA;

(until 14 days after the last PEG-asparaginase administration or 7 days after the last Erwinia asparaginase administration)

Medium Risk Intensification

• restart: in week 1 (on day of first asparaginase administration);

• continued until: week 29



continuous asparaginase schedule

Induction, Protocol M and Medium Risk intensification

• start: day 12 of Induction IA;

• continued until week 17 of MR intensification

In the intervention arm, high prophylactic dose LMWH (nadroparin) is subcutaneously injected daily, adjusted to actual body weight with 85 IU anti-Xa/kg with a maximum of 5700 IU anti-Xa daily. Target anti-Xa level: 0.3-0.4 IU/ml)