Clinical Trials Register

Summary
EudraCT Number:	2012-005804-16
Sponsor's Protocol Code Number:	1256803
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-04-22
Trial 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

2012-005804-16

A.3

Full title of the trial

Front-line therapy with Carfilzomib, Lenalidomide, and Dexamethasone (CRd) induction followed by autologous stem cell transplantation, CRd consolidation and Lenalidomide maintenance in Newly Diagnosed Multiple Myeloma Patients ≤65 years old : a phase II study of the Intergroupe Francophone du Myélome (IFM)

Traitement de première ligne par Carfilzomib, Lenalidomide et Dexamethasone (CRd) en induction suivi par une autogreffe de cellules souches, un traitement de consolidation par CRd et un entretien par Lenalidomide chez les patients de ≤ 65 ans atteints de Myélome Multiple de novo : une étude de phase II de l’Intergroupe Francophone du Myélome (IFM)

A.3.1

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

Traitement de première ligne par Carfilzomib, Lenalidomide et Dexamethasone (CRd) en induction suivi par une autogreffe de cellules souches, un traitement de consolidation par CRd et un entretien par Lenalidomide chez les patients de ≤65 ans atteints de Myélome Multiple de novo : une étude de phase II de l’Intergroupe Francophone du Myélome (IFM)

A.3.2

Name or abbreviated title of the trial where available

IFM CRd

Etude pilote IFM CRd

A.4.1

Sponsor's protocol code number

1256803

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	CHU de Toulouse
B.1.3.4	Country	France
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	Onyx
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Celgene
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHU de Toulouse
B.5.2	Functional name of contact point	Marie Elise Llau
B.5.3	Address:
B.5.3.1	Street Address	2 rue viguerie -Hôtel Dieu
B.5.3.2	Town/ city	TOULOUSE
B.5.3.3	Post code	31059
B.5.3.4	Country	France
B.5.5	Fax number	33(0)561778411

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	REVLIMID (LENALIDOMIDE) 25mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited,
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	MM:EU/3/03/177
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENALIDOMIDE
D.3.9.1	CAS number	191732-72-6
D.3.9.4	EV Substance Code	SUB25389
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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.IMP: 2
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	CARFILZOMIB
D.2.1.1.2	Name of the Marketing Authorisation holder	Onyx pharmaceuticals
D.2.1.2	Country which granted the Marketing Authorisation	United States
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/3/08/548
D.3 Description of the IMP
D.3.1	Product name	CARFILZOMIB
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
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	CARFILZOMIB
D.3.9.1	CAS number	868540-17-4
D.3.9.3	Other descriptive name	CARFILZOMIB
D.3.9.4	EV Substance Code	SUB32911
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
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.IMP: 3
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	REVLIMID (LENALIDOMIDE) 5mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	MM:EU/3/03/177
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENALIDOMIDE
D.3.9.1	CAS number	191732-72-6
D.3.9.4	EV Substance Code	SUB25389
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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

Multiple Myeloma

Myelome Multiple

E.1.1.1

Medical condition in easily understood language

Multiple Myeloma

Myelome Multiple

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

E.2 Objective of the trial

E.2.1

Main objective of the trial

This phase II study is designed to determine whether induction and consolidation treatment with 2 x 4 cycles of Carfilzomib, Lenalidomide and Dexamethasone (CRd), within an intensive program, warrant further investigation in clinical trials.
The primary objective is to evaluate the sCR rate of the combination of carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients at the completion of consolidation therapy

Évaluer le taux de RC stringente à la fin du traitement de
consolidation.

E.2.2

Secondary objectives of the trial

-Determine the safety and tolerability of the drug combination in this patient population as induction and consolidation therapy.
-Evaluate the sCR, CR, VGPR and PR rates after induction, HDM with ASCT, consolidation , during and after maintenance
-Evaluate the overall response rate, time to response, progression free survival, the overall survival, time to progression and duration of response.
-Evaluate the feasibility and quality of the peripheral stem cell collection.

- Déterminer l'innocuité et la tolérance de l’association CRd en
induction et en traitement de consolidation
- Évaluer les taux de sRC, RC, RP et les taux TBRP après l'induction,
l’intensification, la consolidation, pendant et à la fin de l'entretien
- Évaluer le taux de réponse global, la date de réponse, la survie sans
progression, la survie globale, le temps jusqu'à progression et la durée
de la réponse.
- Évaluer la faisabilité et la qualité de la collecte de cellules souches
périphériques.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Age ≥ 18 years and ≤ 65 years at the time of signing informed consent form
-Patients diagnosed with multiple myeloma based on the new International Myeloma Working Group Diagnostic Criteria for plasma cells disorders (Leukemia 2009)
-Subjects must have symptomatic myeloma with CRAB criteria
-Subjects must have measurable disease requiring systemic therapy defined by serum M-component ≥ 5g/l, urine M-component ≥ 200 mg/24h or serum FLC ≥ 100 mg/l.
-Subjects must not have been treated previously with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify the subject
-Life expectancy ≥ 3 months
-ECOG performance status 0–2

- Un âge ≥ 18 ans et ≤ 65 ans au moment de la signature du formulaire
de consentement éclairé
- Un diagnostic de Myélome Multiple selon les Critères diagnostiques
du Groupe de travail
- Un Myélome Multiple symptomatique de novo avec atteinte
organique liée au Myélome ou critères CRAB
- Une maladie mesurable nécessitant un traitement systémique définie
par un composant monoclonal sérique ≥ 5 g / l, ou un composant
monoclonal urinaire ≥ 200 mg/24 h ou des chaines légères libres
sériques ≥ 100 mg / l.
- Les sujets ne doivent pas déjà avoir été traités avec un traitement
systémique pour le myélome multiple. Un traitement antérieur avec des
corticostéroïdes ou de la radiothérapie ne disqualifie pas le sujet.
- Une espérance de vie ≥ 3 mois -
- Un indice de performance ECOG 0-2

E.4

Principal exclusion criteria

-Pregnant or lactating females
-Evidence of mucosal or internal bleeding and/or platelet refractory
-Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment
-Known human immunodeficiency virus infection
-Active hepatitis viral infection and history of hepatitis B or C
-Prior myeloma systemic therapy
- Treatment by localized radiotherapy if the interval between the end of radiotherapy and initiation of protocol therapy lower than 2 weeks.
- Treatment by corticosteroids if exceed the equivalent of 160 mg of dexamethasone in a 2-week period before initiation therapy.
- Subjects not eligible for high dose therapy

- Les femmes enceintes ou qui allaitent
- un syndrome hémorragique cutanéo-muqueux ou interne et/ou état
réfractaire aux transfusions plaquettaires
- une infection aigüe active nécessitant un traitement (antibiotiques,
antiviraux systémiques, ou antifongiques) dans les 14 jours précédant
l'inclusion
- Une infection connue par le virus d'immunodéficience humaine
- Une hépatite virale active et des antécédents d'hépatite B ou C
- Un traitement systémique antérieur du myélome
- Un traitement par radiothérapie localisée si l’intervalle entre la fin de
la radiothérapie et le début du traitement est de moins de 2 semaines
-Un traitement par corticostéroïdes de plus de 160 mg d’équivalent
dexaméthasone dans les 2 semaines
- Une contre indication à l’intensification thérapeutique

E.5 End points

E.5.1

Primary end point(s)

sCR rate of the combination of carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients at the completion of consolidation.

Taux de réponse complète stricte à la fin de la phase de consolidation

E.5.1.1

Timepoint(s) of evaluation of this end point

sCR rate of the combination of carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients at the completion of consolidation..

Fin de la phase de consolidation

E.5.2

Secondary end point(s)

-Safety and tolerability of the drug combination in this patient population as induction and consolidation therapy.
-sCR, CR and VGPR,PR rates after induction, HDM with ASCT, consolidation during and after maintenance
-Overall response rate, progression free survival, the overall survival, time to progression and duration of response, time to response.
-Feasibility and quality of the peripheral stem cells collection.

E.5.2.1

Timepoint(s) of evaluation of this end point

1-induction and consolidation therapy
2-consolidation during and after maintenance
3-NA
4-Stem cells collection

1-Induction et consolidation
2-durant la consolidation et après la maintenance
3-NA
4-Collection de cellules souches

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

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)

Yes

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

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

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

60th month.
the median time survie.Permet meet secondary objectives

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

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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3

Specific vulnerable populations

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

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

none

aucun

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

2013-05-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-04

P. End of Trial
P.	End of Trial Status	Completed

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