Clinical Trials Register

Summary
EudraCT Number:	2014-000554-10
Sponsor's Protocol Code Number:	GEM2014MAIN
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:	2014-05-14
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

2014-000554-10

A.3

Full title of the trial

A randomized, open-label, national multicenter, phase III trial studying maintenance treatment with lenalidomide and dexamethasone versus lenalidomide, dexamethasone and MLN9708 after autologous hematopoietic stem cell transplant in patients with newly-diagnosed, symptomatic multiple myeloma.

Estudio fase III nacional, multicéntrico, abierto, aleatorizado, de tratamiento de mantenimiento con lenalidomida y dexametasona versus lenalidomida, dexametasona y MLN9708 tras trasplante autólogo de progenitores hematopoyéticos para pacientes con mieloma múltiple sintomático de nuevo diagnóstico.

A.3.1

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

A randomized, open-label, national in patients with newly-diagnosed, symptomatic multiple myeloma.

Estudio fase III nacional, para pacientes con mieloma múltiple sintomático de nuevo diagnóstico.

A.4.1

Sponsor's protocol code number

GEM2014MAIN

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	Fundación PETHEMA
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	Fundación PETHEMA
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	TFS
B.5.2	Functional name of contact point	Begoña García
B.5.3	Address:
B.5.3.1	Street Address	Calle Arturo Soria 336, 7I
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28033
B.5.3.4	Country	Spain
B.5.4	Telephone number	34911250550
B.5.5	Fax number	34911250551

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MLN9708, CAPSULES, 4.0 mg
D.3.2	Product code	MLN9708
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	ixazomib
D.3.9.1	CAS number	1239908-20-3
D.3.9.3	Other descriptive name	MLN9708
D.3.9.4	EV Substance Code	SUB31688
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	4.0
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	Revlimid 5mg, cápsulas duras
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE LTD.
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	REVLIMID
D.3.2	Product code	REVLIMID
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.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 10mg, cápsulas duras
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE LTD.
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	REVLIMID
D.3.2	Product code	REVLIMID
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	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.IMP: 4
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 15mg, cápsulas duras
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE LTD.
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	REVLIMID
D.3.2	Product code	REVLIMID
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	15
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: 5
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 25mg, cápsulas duras
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE LTD.
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	REVLIMID
D.3.2	Product code	REVLIMID
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: 6
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MLN9708, CAPSULES, 3.0 mg
D.3.2	Product code	MLN9708
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	ixazomib
D.3.9.1	CAS number	1239908-20-3
D.3.9.3	Other descriptive name	MLN9708
D.3.9.4	EV Substance Code	SUB31688
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	3.0
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: 7
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MLN9708, CAPSULES, 2.3 mg
D.3.2	Product code	MLN9708
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	ixazomib
D.3.9.1	CAS number	1239908-20-3
D.3.9.3	Other descriptive name	MLN9708
D.3.9.4	EV Substance Code	SUB31688
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	2.3
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

Mieloma múltiple

E.1.1.1

Medical condition in easily understood language

Multyple Mieloma

Mieloma múltiple

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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

Impact on progression-free survival (PFS) when adding MLN9708 to post-transplant maintenance treatment with lenalidomide/dexamethasone in patients with multiple myeloma.

Impacto en la supervivencia libre de progresión (SLP) al añadir MLN9708 al tratamiento de mantenimiento postrasplante con lenalidomida/dexametasona en pacientes con mieloma múltiple.

E.2.2

Secondary objectives of the trial

Evaluate development and clinical significance of minimal residual disease (MRD) from the time maintenance treatment is initiated, yearly over five years,
Overall survival (OS)
Evaluate the safety and tolerability of the maintenance treatment

Evaluar la evolución y el significado clínico de la enfermedad mínima residual (EMR) desde el inicio del mantenimiento y anualmente durante 5 años.
Supervivencia global (SG)
Evaluar la seguridad y tolerabilidad del tratamiento de mantenimiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The patient must, in the opinion of the investigator, be capable of complying with all requirements of the trial.
Have signed the informed consent form
Be between 18 and 67 years of age
Have an ECOG Performance Status ? 2 (or 3 if the ECOG is due to myeloma, e.g. pathological fracture)
Multiple myeloma patient who was included in the GEM2012MENOS65 trial, and who is found to have, at a minimum, minimal response after consolidation
Life expectancy > 3 months
The patient must have the following laboratory values in the 21 days prior to initiation of treatment (day 1, cycle 1):
Platelet count ? 100 x 109/L and absolute neutrophil count of ? 1.0 x 109/L. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
Corrected serum calcium < 14 mg/dL.
Aspartate transaminase (AST) and alanine transaminase (ALT) ? 2.5 x the upper limit of normal (ULN)
Total bilirubin within normal range
Calculated creatinine clearance > 30 mL/min
Female patients who:
Are postmenopausal for at least 1 year before the screening visit, OR
Are surgically sterile, OR
If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

El paciente debe, en opinión del investigador, ser capaz de cumplir con todos los requerimientos del ensayo.
Consentimiento informado firmado
Edad entre 18-67 años
Estado funcional ECOG menor o igual a 2 (ó 3 si el ECOG se debe al mieloma, por ej. fractura patológica)
Paciente que haya sido incluído en el ensayo GEM2012MENOS65 y que se encuentre al menos con respuesta mínima tras la consolidación
Esperanza de vida mayor a 3 meses.
El paciente debe tener los siguientes valores de laboratorio en los 21 días previos al inicio del tratamiento (día 1, ciclo 1):
Recuento de plaquetas mayor o igual a 100 x 109/L y recuento absoluto de neutrófilos mayor o igual a 1.0 x 109/L. No se permiten las trasfusiones de plaquetas para cumplir con este criterio de inclusión, .
Calcio sérico corregido menosr a 14 mg/dL.
Aspartato transaminasa (AST) y alanina transaminasa (ALT) menor o igual a 2.5 x el límite superior de normalidad (LSN).
Bilirrubina total dentro de los límites de normalidad.
Aclaramiento de Creatinina estimado mayor a 30 mL/min.
Las pacientes mujeres deberán:
Haber entrado en la menopausia al menos 1 año antes de la visita de selección, O BIEN
Haber sido esterilizadas quirúrgicamente, O BIEN
Si están en edad fértil, deberán estar de acuerdo en utilizar 2 métodos anticonceptivos eficaces (de forma simultánea), desde el momento en el que se firme el consentimiento informado, hasta el 90º día posterior a la última dosis del fármaco del estudio, Y
Deberán seguir las directrices de cualquier programa anticonceptivo específico del tratamiento, si corresponde, O
Deberán estar de acuerdo en practicar una abstinencia real, si ello es una decisión coherente con el estilo de vida de la paciente. (La abstinencia periódica [por ejemplo, por métodos basados en el calendario, la ovulación, variaciones térmicas o la estimación del período posovulatorio] así como el coitus interruptus no son métodos anticonceptivos aceptables).
Los pacientes varones, incluso aquellos que hayan sido sometidos a esterilización quirúrgica (vasectomía), deben comprometerse a cumplir 1 de las siguientes opciones:
Deberán comprometerse a utilizar métodos anticonceptivos de barrera eficaces, tanto durante la totalidad del período de tratamiento del estudio como durante los 90 días posteriores a la última dosis del fármaco del estudio, O
Deberán seguir las directrices de cualquier programa anticonceptivo específico del tratamiento, si se realiza, O
Deberán estar de acuerdo en practicar una abstinencia real, si ello es una decisión coherente con el estilo de vida del paciente. (La abstinencia periódica [por ejemplo, por métodos basados en el calendario, la ovulación, variaciones térmicas o la estimación del período posovulatorio] así como el coitus interruptus no son métodos anticonceptivos aceptables).

E.4

Principal exclusion criteria

Patients not included in clinical trial GEM2012MENOS65
Patients included in GEM2012MENOS65 who are not found to have a least minimal response after consolidation
Patients included in GEM2012MENOS65 who were discontinued prematurely due to toxicity or disease progression
Female patients who are lactating or have a positive serum pregnancy test during the screening period.
Central nervous system involvement
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
Systemic treatment, within 14 days before the first dose of MLN9708, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John?s wort.
Any serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with the completion of treatment according to this protocol.
Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Peripheral neuropathy ? grade 2 in the 21 days prior to inclusion.
Known hypersensitivity to lenalidomide or to MLN9708, their analogues, or excipients in the various formulations of any agent.
Patients who have had a myocardial infarction in the six months prior to inclusion in the clinical trial, or who are class III or IV according to the New York Heart Association (NYHA), heart failure unstable angina, uncontrolled ventricular arrhythmias or acute ischemia detected by electrocardiogram, or conduction disorders.
Patients who are currently participating in another clinical trial or receiving any other investigational product.
Seropositive for HVB, HVC or HIV.

Pacientes no incluidos en el ensayo clínico GEM2012MENOS65
Pacientes incluidos en el GEM2012MENOS65 que no se encuentren al menos con respuesta mínima tras la consolidación.
Pacientes incluidos en el GEM2012MENOS65 y que tuvieron que ser discontinuados prematuramente por toxicidad o por progresión de la enfermedad
Pacientes femeninas que estén en período de lactancia o presenten un resultado positivo en una prueba de embarazo en suero realizada durante el período de selección.
Afectación del sistema nervioso central.
Infección que requiera la administración de un tratamiento con antibióticos sistémicos u otra infección grave, en el transcurso de los 14 días previos al reclutamiento en el estudio.
Tratamiento sistémico con inhibidores potentes del CYP1A2 (fluvoxamina, enoxacina, ciprofloxacina), inhibidores potentes del CYP3A (claritromicina, telitromicina, itraconazol, voriconazol, ketoconazol, nefazodona, posaconazol) o inductores potentes del CYP3A (rifampina, rifapentina, rifabutina, carbamazepina, fenitoína, fenobarbital) o haber recibido Ginkgo biloba o hierba de San Juan en el transcurso de los 14 días previos a la primera dosis de MLN9708.
Presentar una enfermedad grave (incluidos los trastornos psiquiátricos) que, en opinión del investigador, pudiera interferir con el cumplimiento terapéutico del paciente, de acuerdo con este protocolo.
Enfermedad o procedimiento GI que pueda interferir con la absorción oral u tolerancia de MLN9708, incluida la dificultad para tragar.
Haber sido diagnosticado o haber recibido tratamiento para otra neoplasia maligna en el transcurso de los 2 años previos al reclutamiento en el estudio, o haber sido diagnosticado previamente con otra neoplasia maligna y presentar indicios de enfermedad residual. No se excluirá a los pacientes con cáncer de piel no melanomatoso o carcinoma in situ de cualquier tipo, siempre que se hayan sometido a una resección completa.
Neuropatía periférica mayor a grado 2 dentro de los 21 días previos a su inclusión.
Hipersensibilidad conocida a la lenalidomida o al MLN9708, fármacos análogos o excipientes presentes en diversas formulaciones de los mismos.
Paciente que haya tenido un infarto de miocardio en los 6 meses previos a la inclusión en el ensayo clínico o posea una clase funcional III o IV de acuerdo con la New York Heart Association (NYHA), insuficiencia cardiaca, angina no controlada, arritmias ventriculares no controladas o isquemia aguda detectada electrocardiográficamente o trastornos del sistema de conducción.
Pacientes que estén actualmente en otro ensayo clínico o recibiendo cualquier agente en investigación.
Serología positiva para VHB, VHC o VIH.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS) after the two maintenance regimens.

Supervivencia libre de progresión (SLP) tras los dos regímenes de mantenimiento.

E.5.1.1

Timepoint(s) of evaluation of this end point

60 months

60 meses

E.5.2

Secondary end point(s)

Sequential negative minimal residual disease studies (MRD) at the start of treatment and then yearly for five years.
Overall survival from the time treatment is initiated.
Evaluate the safety and tolerability of the maintenance treatment

Estudios secuenciales de enfermedad mínima residual negativa (EMR) al inicio y anual durante 5 años.
Supervivencia global desde el inicio del mantenimiento.
Evaluar la seguridad y tolerabilidad del tratamiento de mantenimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

60 months

60 meses

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

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

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

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

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

LPLV

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:

316

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

316

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)

There are not

No hay

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

2014-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-06-17

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