Main 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 during asparaginase treatment.Secondary objectives:1…
ID
Source
Brief title
Condition
- Leukaemias
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of symptomatic objectified VTE during childhood ALL treatment in the
intervention and standard arm during asparaginase treatment.
Secondary outcome
1. Incidence of major bleeding in the intervention and standard arm during
asparaginase treatment.
2. Incidence of the clinically relevant non-major bleeding and minor bleeding
in the intervention and standard arm during asparaginase treatment.
3. Incidence of composite of asymptomatic and symptomatic objectified VTE
during childhood ALL treatment in the intervention and standard arm during
asparaginase treatment.
4. Identification of clinical risk factors and hematological biomarkers in
consecutively included patients with and without VTE; to increase insight
in the pathogenesis of coagulation disorders during ALL treatment, and to
establish a risk model for VTE
Background summary
Venous thromboembolism (VTE) often complicates the treatment of acute
lymphoblastic leukemia (ALL), particularly during asparaginase therapy.
Study objective
Main 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 during asparaginase treatment.
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
major bleeding during asparaginase treatment.
2. 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.
Study design
A national, multi-centre, randomized controlled, open-label trial.
Intervention
Intervention-arm:
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).
Standard of care-arm:
The comparator treatment in the standard of care control arm is no systemic
thromboprophylaxis, i.e. no intervention, which is the current standard during
childhood ALL treatment. Placebo injections will not be applied.
Study burden and risks
The route of administration is by subcutaneous injections; by
self-administration or by administration by their parents / caretakers or
nurses. The burden is that patients will have to receive or administer
subcutaneous injections for the entire duration of asparaginase therapy.
Pain of subcutaneous injections can be relieved by using anesthetic creme (EMLA
creme) or by using insuflon, a subcutaneous catheter.
Zinkwerf 5-7
Den Haag 2544 EC
NL
Zinkwerf 5-7
Den Haag 2544 EC
NL
Listed location countries
Age
Inclusion criteria
a. Written informed consent for TropicALL randomisation has been given
b. Newly diagnosed patients with T-lineage or precursor-B lineage ALL (patients with mature B-ALL are not eligible)
c. Age between * 366 days and < 19 years
d. Diagnosis ALL confirmed by DCOG laboratory
e. Patient should be treated in a Dutch Childhood Oncology Centre
Exclusion criteria
a. Patients who are already being treated with anticoagulation upon screening (for other indications)
b. Patients with a heparin allergy (or for one of its components), a recent history (within 6 months) of heparin-induced thrombocytopenia (HIT) or any other contraindication listed in the local labeling of LMWH
c. Patients with active bleeding or high risk for bleeding contraindicating anticoagulant therapy (Thrombocytopenia is not an exclusion criterion)
d. Patients with renal insufficiency (glomerular filtration rate (GFR) < 30 ml/min/1.73m2)
e. Patients with hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk
f. Patients with stage 2 hypertension defined as blood pressure confirmed > 99th percentile + 5 mmHg
g. Patients with any condition that, as judged by the investigator, would place the patient at increased risk of harm if he/she participated in the study.
h. Patients who are included in the ALL-11 IVIG study
i. Patients with Ph-positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR/ABL fusion transcript). These patients will be transferred to the EsPhALL protocol in induction according to the guidelines of the EsPhALL protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003303-30-NL |
| CCMO | NL50440.078.14 |