Clinical Trials Register

Summary
EudraCT Number:	2014-001330-29
Sponsor's Protocol Code Number:	LENALID01
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-16
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

Spain - AEMPS

A.2

EudraCT number

2014-001330-29

A.3

Full title of the trial

Ensayo piloto aleatorizado de dosis habitual de lenalidomida vs reducción de dosis
en pacientes con mieloma múltiple en recaída que han alcanzado máxima
respuesta.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Mantenimiento Lenalidomida

A.4.1

Sponsor's protocol code number

LENALID01

A.5.4

Other Identifiers

Name:

Number:

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	Ernesto Pérez Persona
B.1.3.4	Country	Spain
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	No
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ernesto Pérez Persona
B.5.2	Functional name of contact point	Servicio hematología
B.5.3	Address:
B.5.3.1	Street Address	Jose Atxotegi, s/n
B.5.3.2	Town/ city	Vitoria-Gasteiz
B.5.3.3	Post code	01009
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3494500 71 71
B.5.5	Fax number	+3494500 73 80
B.5.6	E-mail	ernesto.perezpersona@osakidetza.net

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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
D.2.1.1.2	Name of the Marketing Authorisation holder	REVLIMID
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Lenalidomida
D.3.2	Product code	LENA25
D.3.4	Pharmaceutical form	Capsule
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.3.9.2	Current sponsor code	LENA25
D.3.9.3	Other descriptive name	LENALIDOMIDA
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	Comparator
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	Dexametasona
D.2.1.1.2	Name of the Marketing Authorisation holder	Dexametasona
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Dexametasona
D.3.2	Product code	DEXA40
D.3.4	Pharmaceutical form	Capsule
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	DEXAMETHASONE
D.3.9.2	Current sponsor code	DEXA40
D.3.9.3	Other descriptive name	DEXAMETASONA
D.3.9.4	EV Substance Code	SUB07017MIG
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	40
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
D.2.1.1.2	Name of the Marketing Authorisation holder	REVLIMID
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Lenalidomida
D.3.2	Product code	LENA10
D.3.4	Pharmaceutical form	Capsule
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.3.9.2	Current sponsor code	LENA10
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	10
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

Mieloma múltiple en recaída

E.1.1.1

Medical condition in easily understood language

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	16.1
E.1.2	Level	HLT
E.1.2	Classification code	10028229
E.1.2	Term	Multiple myelomas
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Compare disease-free survival between patients with lenalidomide at low-dose and patients with lenalidomide at standard dose and dexamethasone

.- Comparar la SLP entre lenalidomida a dosis bajas de mantenimiento y lenalidomida y
dexamesasona a dosis estándar.
.

E.2.2

Secondary objectives of the trial

Compare the effectiveness in terms of response rate , duration of response, time to progression (TTP) and overal survivall (OS) of both schemes of treatment.
Determine the percentaje of pacients of both limbs who achieve complete response (CR) once observed biologic progression.
Compare the safety and tolerability of both schemes.

- Comparar la eficacia en términos de respuesta, duración de la respuesta, tiempo hasta
progresión (TTP)) y supervivencia global (SG) de ambos esquemas.
.- Determinar el porcentaje de pacientes de ambas ramas que consiguen RC una vez
observada progresión biológica.
.- Comparar la seguridad y tolerabilidad de ambos esquemas

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must voluntarily sign informed consent before performing any test of study that is not part of routine care of patients.
Furthermore patients must be informed about the right of leaving the study at any moment and without detriment of subsequent care.
The patient must be diagnosed of symptomatic multiple myeloma according to established criteria.
Multiple myeloma with measurable disease at the time of relapse, according to the international criteria and for which doctor considers indicated the treatment with lenalidomide (25 mg / day) and dexamethasone (dexamethasone pulses or weekly dexamethasone).
At the time of relapse must have filed measurable disease defined as follows:
For secretory Multiple Myeloma measurable disease is defined by the presence of measurable monoclonal serum component superior or equal to 1 g / dL, or in urine when light chain excretion is superior or equal to 200 mg / 24 hours.
For oligo secretory or nonsecretory Multiple Myeloma, serum levels of free light chain
affected, superior or equal to 10 mg / dL (erior or equal to 100 mg / L, with a ratio of abnormal free light chain serum)
At the time of randomization the patient should be receiving a dose of lenalidomide superior or equal to 10 mg / day, at least 5 mg weekly dexamethasone.
Randomization was performed at the time it has reached maximum response with lenalidomide and dexamethasone, defined as follows:
· CR with negative IFE. Once objectified the RC, this should be confirmed at 8 weeks, during which time the patient will continue without change the dose of lenalidomide and
dexamethasone. That is, once RC is documented, patients receive two cycles of lenalidomide and dexamethasone until confirmation of the same.
· PR phase "Plateau", defined as at least 3 months with a stable monoclonal component, and have completed at least one year of treatment with lenalidomide and dexamethasone.
The patient should have the following laboratory values ??prior to corresponding induction treatment initiation:
: Platelet count erior or equal to 50,000 / mm3, hemoglobin erior or equal to 8 g / dl and counting
absolute neutrophil erior or equal to 1000 / mm3. Lower values ??are permitted if they are due to infiltration of the MO

El paciente debe firmar voluntariamente el consentimiento informado antes de la realización de cualquier prueba del estudio que no forme parte de la atención habitual de los pacientes, con el conocimiento por parte del paciente de que puede abandonar el estudio en el momento que quiera,
sin que se vea perjudicado en ningún momento su atención posterior.
El paciente debe estar diagnosticado de Mieloma Múltiple sintomático según los criterios establecidos.
Mieloma múltiple con enfermedad medible en el momento de la recaída, según los criterios
internacionales y para el que su médico considera indicado tratamiento con lenalidomida (25 mg/día)
y dexametasona (pulsos de dexametasona o dexametasona semanal). En el momento de la recaída
debe haber presentado enfermedad medible definida como sigue:
Para Mieloma Múltiple secretor, la enfermedad medible es definida por la presencia de componente monoclonal superior o igual a 1g/dL o, en orina si la excreción de cadenas ligeras es superior
o igual a 200 mg/24 horas.
Para Mieloma Múltiple oligo secretor o no secretor, nivel en suero de la cadena ligera libre afectada superior o igual 10 mg/dL (superior o igual 100 mg/L, con una ratio de cadenas ligeras libres en suero anormal)
En el momento de la aleatorización el paciente debe estar recibiendo una dosis de lenalidomida superior o igual a 10 mg/día y al menos 5 mg semanales de dexametasona.
La aleatorización se realizará en el momento en que se ha alcanzado máxima respuesta con lenalidomida y dexametasona, definida como sigue:
· RC con IFE negativa. Una vez objetivada la RC, esta se ha de confirmar a las 8 semanas, tiempo durante el cual el paciente continuará sin modificar la dosis de lenalidomida y
dexametasona. Es decir, una vez que se documente RC, el paciente recibirá dos ciclos más de lenalidomida y dexametasona hasta la confirmación de la misma.
· RP en fase de"plateau", definida como al menos 3 meses con un CM estable, y haber cumplido al menos un año de tratamiento con lenalidomida y dexametasona.
El paciente debe tener los siguientes valores de laboratorio previamente al inicio del tratamiento de
inducción correspondiente: Recuento de plaquetas superior o igual a 50000/mm3, hemoglobina superior o igual a 8 g/dl y recuento
absoluto de neutrófilos superior o igual a 1000/mm3. Valores más bajos están permitidos si son debidos a infiltración de la MO

E.4

Principal exclusion criteria

Patients in second or subsequent relapses. Patients may have received only treatment for newly diagnosed multiple myeloma. Is allowed at the time of relapse;
- steroid treatment pulses for some urgency required prior to initiating
second-line treatment,
-administration of bisphosphonates or antialgic radiotherapy due to the presence of plasmacytomas
Patients with non-measurable disease or by SFLC.
Patients with known hypersensitivity to lenalidomide.
Patients who have received any investigational agent within 30 days prior to enrollment.
Patients receiving doses below 10 mg / day of lenalidomide
Dexamethasone intolerant patients.
Patients who are currently in another clinical trial or receiving any investigational agent.
Hypertension or poorly controlled diabetes mellitus or other serious organic disease involving excessive risk to the patient or any psychiatric disorder interfering with the understanding of informed consent

Los pacientes que presenten alguno de los siguientes criterios de exclusión no podrán ser incluidos
en el estudio clínico:
Pacientes en segunda recaída o posteriores. Los pacientes únicamente pueden haber recibido tratamiento para Mieloma Múltiple de nuevo diagnóstico. Se permite en el momento de la recaída tratamiento con pulsos de esteroides por alguna urgencia que lo requiera previo a iniciar el
tratamiento en segunda línea, la administración de bisfofonatos o radioterapia bien antiálgica o debido a la presencia de plasmocitomas que la requieran por alguna urgencia.
Pacientes con enfermedad no medible ni por sFLC.
Pacientes con hipersensibilidad conocida a lenalidomida.
Pacientes que hayan recibido cualquier agente en investigación en los 30 días previos a su inclusión.
Pacientes que estén recibiendo dosis inferiores a 10 mg/ día de lenalidomida
Pacientes intolerantes a dexametasona.
Pacientes que estén actualmente en otro ensayo clínico o recibiendo cualquier agente en investigación.
Hipertensión arterial o diabetes mellitus mal controladas o cualquier otra enfermedad orgánica grave que suponga un riesgo excesivo para el paciente o cualquier alteración psiquiátrica que interfira con la comprensión del consentimiento informado.

E.5 End points

E.5.1

Primary end point(s)

Primary efficacy endpoint: progression-free survival (PFS) from the date of initiation of lenalidomide up to the date of disease progression or death from any cause.
Safety and tolerability of the proposed schemes: key safety variables.

Variable principal de eficacia: supervivencia libre de progresión (SLP) desde la fecha de inicio de tratamiento con lenalidomida hasta la hasta la fecha de la progresión de la enfermedad o muerte debido a cualquier causa.
Variables principales de seguridad: seguridad y tolerabilidad de los esquemas propuestos.

E.5.1.1

Timepoint(s) of evaluation of this end point

At two years, at progression moment or at death moment due any cause. The first thing is

A los dos años, al momento de la progresión o muerte, lo primero

E.5.2

Secondary end point(s)

Variables secundarias de eficacia: eficacia, en términos de tasa de respuestas, duración de la respuesta, TTP y SG en ambos grupos de tratamiento.
Determinar la causa de muerte de los pacientes, y determinar el grado de relación con el MM o el
tratamiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints: efficacy in terms of response rate, duration of response, TTP and OS in both treatment groups.
Determining the cause of death of patients, and its relationship with the MM or
treatment.

A los dos años, al momento de la progresión o muerte, lo primero

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

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

Lenalidomida 25mg

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

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)

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)

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

2015-01-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-01-27

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