Clinical Trials Register

Summary
EudraCT Number:	2014-003303-30
Sponsor's Protocol Code Number:	2014-003303-30
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-11-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2014-003303-30

A.3

Full title of the trial

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

TropicALL studie; Tromboprofylaxe in kinderen behandeld voor Acute lymfatische leukemie met laag-moleculair-gewicht heparine: een gerandomiseerde studie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

TropicALL study

TropicALL studie

A.4.1

Sponsor's protocol code number

2014-003303-30

A.5.4

Other Identifiers

Name:

NTR number

Number:

4707

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Dutch Childhood Oncology Group
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Dutch Childhood Oncology Group
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Nederlandse organisatie voor gezondheidsonderzoek en zorginnovatie (ZonMw)
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dutch Childhood Oncology Group
B.5.2	Functional name of contact point	Trial and Data Center
B.5.3	Address:
B.5.3.1	Street Address	PO-box 43515
B.5.3.2	Town/ city	The Hague
B.5.3.3	Post code	2504 AM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031703674545
B.5.5	Fax number	0031703598718
B.5.6	E-mail	trialbureau@skion.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fraxiparine
D.2.1.1.2	Name of the Marketing Authorisation holder	Aspen Pharma Trading Limited
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fraxiparine
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute lymphoblastic leukemia

Acute lymfatische leukemie

E.1.1.1

Medical condition in easily understood language

Bloodcancer

Bloedkanker

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10000845
E.1.2	Term	Acute lymphoblastic leukemia
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

Het bepalen van de effectiviteit van tromboprofylaxe met hoge profylactische dosis laag-moleculair-gewicht heparine (LMWH) in vergelijking met standaard behandeling, i.e. geen tromboprofylaxe in kinderen behandeld voor ALL gedurende asparaginase behandeling.

E.2.2

Secondary objectives of the trial

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 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.

1. Het bepalen van de veiligheid van tromboprofylaxe met hoge profylactische dosis LMWH in vergelijking met standaard behandeling,
i.e. geen tromboprofylaxe in kinderen behandeld voor ALL, door het bepalen van de incidentie van ernstige bloedingen gedurende asparaginase behandeling.
2. Het bepalen of tromboprofylaxe met hoge profylactische dosis LMWH in vergelijking met standaard behandeling, i.e. geen tromboprofylaxe, de
complete remissie en de overleving (overall en ziekte-vrij) beïnvloedt bij kinderen met ALL.
3. Het identificeren van klinische risicofactoren en/of hematologische biomarkers in ALL patiënten met en zonder symptomatische veneuze
trombose om meer inzicht te verkrijgen in de pathogenese van trombose tijdens ALL behandeling en om een risicomodel te ontwikkelen.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All patients between 1 and 19 years of age with primary ALL, who are eligible for and treated within the DCOG ALL-11 or ALL-12 study protocol.

Alle patiënten tussen 1 en 19 jaar oud met primaire ALL, die behandeld worden volgens het SKION ALL-11 en ALL-12 protocol.

E.4

Principal 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 without informed consent
d. Patients with active bleeding or high risk for bleeding contraindicating anticoagulant therapy (Thrombocytopenia is not an exclusion criterion)
e. Patients with renal insufficiency (glomerular filtration rate (GFR) < 30 ml/min/1.73m2)
f. Patients with hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk
g. Patients with stage 2 hypertension defined as blood pressure confirmed > 99th percentile + 5 mmHg
h. 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.

a. Patiënten die al worden behandeld met antistollingsmiddel bij screening (voor andere indicaties)
b. Patiënten met een allergie voor heparine (of voor een van de componenten), een recente geschiedenis (binnen 6 maanden) van heparine-geïnduceerde trombocytopenie (HIT) of elke andere contra-indicatie die genoemd staat in de bijsluiter van LMWH
c. Patiënten zonder informed consent
d. Patiënten met ernstige bloedingen of hoog risico op bloedingen door behandeling met antistollingsmiddel (Thrombocytopenia is geen exclusie criterium)
e. Patiënten met nierinsufficiëntie (glomerulaire filtratiesnelheid (GFR) < 30 ml/min/1.73m2)
f. Patiënten met hepatische ziekte wat geassocieerd wordt met coagulopathie leidend tot een klinisch relevant risico op bloedingen
g. Patiënten met stadium 2 hypertensie gedefinieerd als bevestigde bloeddruk > 99ste percentiel + 5 mmHg
h. Patiënten met elke conditie die, zoals beoordeeld door de onderzoeker, de patiënt een verhoogd risico op nadelige effecten geeft als hij/zij meedoet aan de studie

E.5 End points

E.5.1

Primary end point(s)

Incidence of symptomatic objectified VTE during childhood ALL treatment in the intervention and standard arm during asparaginase treatment.

De incidentie van symptomatische geobjectiveerde veneuze tromboembolie tijdens behandeling van ALL in de interventie- en standaard arm gedurende asparaginase behandeling.

E.5.1.1

Timepoint(s) of evaluation of this end point

During interim analyses and also at the end of this protocol, expected in 2019.

Gedurende interim analyses en aan het eind van dit protocol, verwachting 2019.

E.5.2

Secondary end point(s)

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. ALL treatment outcomes by assessment of complete remission and (overall or disease-free) survival rates in the intervention and standard arm;
5. 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

1. Incidentie van ernstige bloedingen in de interventie- en standaard arm gedurende asperaginase behandeling
2. Incidentie van klinisch relevante bloedingen en kleine bloedingen in de interventie- en standaard arm gedurende asperaginase behandeling
3. Incidentie van de samengestelde uitkomst van asymptomatische en symptomatische geobjectiveerde veneuze trombo-embolie tijdens
behandeling van ALL in de interventie- en standaard arm gedurende asperaginase behandeling
4. ALL behandelingsuitkomsten zoals bepaald door de complete remissie aantallen en overlevings aantallen (overall en ziekte-vrije) in
beide armen
5. Klinische risicofactoren en/of biomarkers in patiënten met en zonder veneuze trombose.

E.5.2.1

Timepoint(s) of evaluation of this end point

During interim analyses and also at the end of this protocol, expected in 2019.

Gedurende interim analyses en aan het eind van dit protocol, verwachting 2019.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

De kinderen in de standaard behandeling arm krijgen geen tromboprofylaxe.

The comparator treatment in the standard of care control arm is no systemic thromboprophylaxis.

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

All patients will be prospectively followed until 3 months after the end of the ALL-11 or 12 treatment period, until recurrence of ALL or until death, whatever endpoint comes first.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1