Clinical Trials Register

Summary
EudraCT Number:	2015-004625-14
Sponsor's Protocol Code Number:	1230.28
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2016-04-26
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

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2015-004625-14

A.3

Full title of the trial

Open-label, dose-escalating trial to evaluate the tolerability, toxicity, safety, pharmacokinetics, pharmacodynamics and activity of volasertib added to the standard intensive salvage chemotherapy regimen with liposomal daunorubicine, fludarabine and cytarabine (DNX-FLA) followed by fludarabine and cytarabine (FLA) in children from 3 months to less than 18 years of age with acute myeloid leukaemia after failure of the front-line therapy

Etude en ouvert, en escalade de dose, visant à évaluer la tolérabilité, la toxicité, la tolérance, la pharmacocinétique, la pharmacodynamie et l’activité du volasertib administré en plus d’une chimiothérapie de rattrapage associant daunorubicine liposomale, fludarabine et cytarabine (DNX-FLA) suivie de l’association fludarabine et cytarabine (FLA) chez des enfants de 3 mois à moins de 18 ans ayant une leucémie myéloïde aiguë après échec d’une chimiothérapie de première ligne.

A.3.1

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

A study to find a safe dose of volasertib given in addition to standard salvage chemotherapy in children (age 3 months to less than 18 years) with acute myeloid leukaemia, in whom front-line chemotherapy failed

Etude pour trouver la dose de volasertib la mieux tolérée en plus d’une chimiothérapie standard de rattrapage chez des enfants (de 3 mois à moins de 18 ans) ayant une leucémie myéloïde aiguë après échec d’une chimiothérapie de première ligne

A.4.1

Sponsor's protocol code number

1230.28

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/246/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	BOEHRINGER INGELHEIM
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Boehringer Ingelheim
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Boehringer Ingelheim Pharma GmbH & Co. KG
B.5.2	Functional name of contact point	QRPE PSC CT Information Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Binger Strasse 173
B.5.3.2	Town/ city	Ingelheim am Rhein
B.5.3.3	Post code	55216
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49800243 0127
B.5.5	Fax number	+49800821 7119
B.5.6	E-mail	clintriage.rdg@boehringer-ingelheim.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/14/1255
D.3 Description of the IMP
D.3.1	Product name	volasertib
D.3.2	Product code	BI 6727
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	volasertib
D.3.9.2	Current sponsor code	BI 6727
D.3.9.3	Other descriptive name	BI 6727
D.3.9.4	EV Substance Code	SUB129714
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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

E.1.1.1

Medical condition in easily understood language

Acute myeloid leukaemia after failure of front-line therapy in paediatric patients

Leucémie myéloïde aiguë après échec d'un traitement de première ligne chez des patients en pédiatrie

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

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 define the MTD and/or dose to be used for further development by evaluation of DLT in course 1 and the safety of volasertib when added to standard intensive salvage chemotherapy with DNX-FLA in paediatric patients with AML after failure of first-line therapy

Définir la dose maximale tolérée et/ou la dose à utiliser pour le développement futur en évaluant les « toxicités dose limitante » DLT au cours du cycle 1 et la tolérance du volasertib administré en plus d’une chimiothérapie standard intensive de rattrapage (DNX-FLA) chez des enfants en pédiatrie ayant une leucémie myéloïde aiguë après échec d’une thérapie de première ligne.

E.2.2

Secondary objectives of the trial

To collect data on efficacy and PK/PD of volasertib in paediatric patients with AML when added to standard intensive salvage chemotherapy

Obtenir des données d’efficacité et des données pharmacocinétiques PK/pharmacodynamiques PD du volasertib administré en plus d’une chimiothérapie standard intensive de rattrapage, chez des patients en pédiatrie ayant une leucémie myéloïde aiguë

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients 3 months to <18 years of age at the time of informed consent
- Patients with AML after failure of the front-line intensive AML therapy
- Lansky score at screening =50 for patients from 3 months to <12 years
- Karnofsky score at screening =50 for patients from 12 to <18 years
- Use of highly effective methods of birth-control, if sexually active
- Parents/legal guardians and patients have given written informed consent and informed assent suitable for the respective age group

- Patients de 3 mois à moins de 18 ans lors de la signature du consentement éclairé
- Patients ayant une leucémie myéloïde aiguë après échec d’une chimiothérapie de première ligne
- Score de Lansky lors de la sélection ≥ 50 pour les enfants de 3 mois à < 12 ans
- Score de Karnofsky lors de sélection ≥ 50 pour les enfants de 12 ans à < 18 ans
- Recours à une méthode de contraception efficace, si activité sexuelle
- Consentement éclairé donné par les parents/représentants légaux et assentiment des patients en fonction de l’information donnée par groupe d’âge

E.4

Principal exclusion criteria

- Down syndrome
- Acute promyelocytic leukaemia and treatment-related AML
- QTc prolongation
- LVSF <30%
- Cardiac disease and/or dysfunction
- Active uncontrolled infection
- HIV infection, acute or chronic hepatitis
- Inadequate lab parameters
- Impaired renal function
- Pregnancy or nursing

- syndrome de Down
- leucémie aiguë promyélocytaire et AML reliée à un traitement
- prolongation de l’intervalle QTc
- FRVG < 30%
- maladie cardiaque et/ou dysfonction
- infection active non contrôlée
- infection VIH, hépatite aiguë ou chronique
- fonction rénale anormale
- grossesse ou allaitement

E.5 End points

E.5.1

Primary end point(s)

1: Determination of the MTD of volasertib or the recommended volasertib dose for further studies in combination with standard salvage therapy in paediatric patients with AML after failure of the front-line intensive chemotherapy regimen

1 : Détermination de la DMT du volasertib ou dose recommandée pour les futures études en association à une chimiothérapie standard de rattrapage chez des patients en pédiatrie ayant une LMA après échec d’une chimiothérapie de première ligne

E.5.1.1

Timepoint(s) of evaluation of this end point

1: 4 weeks

4 semaines

E.5.2

Secondary end point(s)

1: Number of patients with clinically relevant lab value changes of calcium (hyper- and/or hypocalcaemia) as judged by the investigator and reported as adverse events (CTCAE grade 3 or higher)

2: Number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations (i.e. AEs)

3: Anti-leukaemic activity of volasertib in combination with standard salvage therapy

4: Event-free survival (EFS)

5: Overall survival (OS)

6: Pharmacokinetic evaluation of volasertib

1. Nombre de patients ayant des changements dans les valeurs de la calcémie pertinents cliniquement (hyper- et/ou hypocalcémie) selon l’investigateur et reportés en tant qu’événements indésirables (CTCAE grade 3 ou plus)
2. Nombre de patients avec des modifications de l’activité cardiaque (intervalle QTc prolongé) reportées comme observations pertinentes (événements indésirables)
3. Activité anti-leucémique du volasertib en association à un traitement standard de rattrapage
4. Survie sans événement (EFS)
5. Survie globale (OS)
6. Evaluation pharmacocinétique du volasertib

E.5.2.1

Timepoint(s) of evaluation of this end point

1: 8 weeks

2: 8 weeks

3: 8 weeks

4: up to 5 years

5: up to 5 years

6: 8 weeks

1. 8 semaines

2. 8 semaines

3. 8 semaines

4. Jusqu’à 5 ans

5. Jusqu’à 5 ans

6. 8 semaines

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Information not present in EudraCT

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Yes

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

LVLS

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Children

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will be treated according to clinical practice.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-04-07

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

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