Clinical Trials Register

Summary
EudraCT Number:	2014-002948-40
Sponsor's Protocol Code Number:	GEM-CESAR
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-02-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2014-002948-40

A.3

Full title of the trial

A phase II multicenter study of carfilzomib, lenalidomide and dexamethasone (KRd) plus high-dose therapy with melphalan-200 and autologous stem cell transplantation, followed by consolidation with KRd, and maintenance with lenalidomide and dexamethasone in patients with high risk smoldering multiple myeloma (SMM) under 65 years

Estudio fase II multicentrico de carfilzomib, lenalidomida y dexametasona (KRd) como induccion, seguido de melfalan a altas dosis y trasplanteautólogo de celulas progenitoras de sangre periferica, consolidacion con KRd y mantenimiento con lenalidomida y dexametasona en pacientes de edad inferior a 65 años con Mieloma Multiple asintomatico de alto riesgo de progresion a Mieloma sintomatico

A.3.1

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

A study of carfilzomib, lenalidomide and dexamethasone (KRd) plus high-dose therapy with melphalan-200 and autologous stem cell transplantation, followed by consolidation with KRd, and maintenance with lenalidomide and dexamethasone in patients with high risk smoldering multiple myeloma (SMM) under 65 years

Estudio de carfilzomib, lenalidomida y dexametasona (KRd) , seguido de melfalan a altas dosis y trasplanteautólogo de celulas progenitoras de sangre periferica, consolidacion con KRd y mantenimiento con lenalidomida y dexametasona en pacientes de edad inferior a 65 años con Mieloma Multiple asintomatico de alto riesgo de progresion a Mieloma sintomatico

A.3.2

Name or abbreviated title of the trial where available

GEM-CESAR

A.4.1

Sponsor's protocol code number

GEM-CESAR

A.5.4

Other Identifiers

Name:

RV-MM-PI-0123

Number:

IST-2013-100651

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	CELGENE S.L.
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Onyx Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dynamic S.L.
B.5.2	Functional name of contact point	Ángel Pérez Romero
B.5.3	Address:
B.5.3.1	Street Address	C/ Azcona 31
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28028
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034914561105
B.5.5	Fax number	0034914561126
B.5.6	E-mail	a.perez@dynasolutions.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	Yes
D.2.1.1.1	Trade name	Revlimid 25 mg hard capsules
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	CC-5013
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.3.9.3	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	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 15 mg hard capsules
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	CC-5013
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.3.9.3	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	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: 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 10 mg hard capsules
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	CC-5013
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.3.9.3	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	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 5 mg hard capsules
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	CC-5013
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.3.9.3	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	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: 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	Kyprolis
D.2.1.1.2	Name of the Marketing Authorisation holder	Onyx Pharmaceuticals, Inc
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	Kyprolis
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 milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
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	Yes
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	Dexamethasone
D.3.4	Pharmaceutical form	Tablet
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.3.9.3	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	range
D.3.10.3	Concentration number	1 to 8
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	Yes
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	Dexamethasone
D.3.4	Pharmaceutical form	Tablet
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.3.9.3	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	range
D.3.10.3	Concentration number	1 to 8
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: 8
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.2.1.2	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	Dexamethasone
D.3.4	Pharmaceutical form	Tablet
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.3.9.3	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	range
D.3.10.3	Concentration number	1 to 8
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: 9
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.2.1.2	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	Melphalan
D.3.4	Pharmaceutical form	Lyophilisate and solvent 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	Melphalan
D.3.9.1	CAS number	3223-07-2
D.3.9.3	Other descriptive name	MELPHALAN HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB126965
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	50
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

Smoldering multiple myeloma

Mieloma múltiple asintomático

E.1.1.1

Medical condition in easily understood language

Multiple myeloma

Mieloma múltiple

E.1.1.2

Therapeutic area

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

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	10028228
E.1.2	Term	Multiple myeloma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the rate of patients achieving and maintaining immunophenotypic response (Flow-CR) (complete response with minimal residual disease negative by multiparametric flow cytometry) at day +100 after high-dose therapy and autologous stem cell transplantation (HDT-ASCT).

Evaluar la tasa de pacientes en respuesta inmunofenotípica (es decir, respuesta completa, sin enfermedad mínima residual (EMR) , utilizando citometría de flujo multiparamétrica) el día +100, tras recibir quimioterapia a altas dosis seguido de trasplante autólogo de progenitores de sangre periférica (HDT-ASCT, por sus siglas en inglés).

E.2.2

Secondary objectives of the trial

1.-To evaluate the rate of patients achieving and maintaining Flow-CR at 3 and 5 years (complete response with minimal residual disease negative by multiparametric flow cytometry after induction, HDT-ASCT, consolidation and maintenance therapy.
2.-To evaluate the efficacy in terms of conventional responses categories: stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR).
3.-To evaluate the time to progression to symptomatic disease (TTP).
4.-To evaluate the Progression-Free Survival (PFS).
5.-To evaluate the Overall Survival (OS).
6.-To evaluate the safety profile.

1.-Evaluar la tasa de pacientes en respuesta inmunofenotípica (es decir, respuesta completa, sin enfermedad mínima residual, utilizando citometría de flujo multiparamétrica) a los 3 y 5 años tras el trasplante.
2.-Evaluar la eficacia, en términos de respuesta: respuesta completa estricta (RCe), respuesta completa (RC), muy buena respuesta parcial (MBRP) y respuesta parcial (RP).
3.-Evaluar el tiempo transcurrido hasta la progresión a enfermedad sintomática (TTP).
4.-Evaluar la supervivencia libre de progresión (SLP).
5.-Evaluar la supervivencia global (SG).
6.-Evaluar el perfil de seguridad a lo largo de las diferentes fases del ensayo: inducción, altas dosis de melfalán seguido de trasplante autólogo, consolidación y mantenimiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.-In the investigator's opinion, the patient must be able to fulfill all the clinical trial requirements.
2.-The patient must voluntarily sign the informed consent before any study procedure that is not part of the standard of care for these patients is performed, with the patient's knowledge that he/she may withdraw from the study at any time, without prejudice to his/her future care.
3.-Age older than 18 and younger than 65 years and candidates to receive high-dose therapy and autologous stem cell transplantation.
4.-The patient must be diagnosed with smoldering MM at high risk of progressing to symptomatic MM, or at ultra high risk of progression to symptomatic disease, defined by:
- SMM at high risk of progression to symptomatic disease:
a. Bone marrow infiltration with plasma cells (PCs) greater than or equal 10% and presence of a monoclonal component, IgG greater than3 g/dL or IgA greater than 2 g/dL or Bence Jones proteinuria greater than 1 g/24h and absence of lytic lesions, hypercalcemia, renal failure (creatinine less than 2 mg/dL) and anemia (hemoglobin greater than 10 gr/dL or not 2 gr/dL below the lower limit of normal).
b. Bone marrow infiltration with PCs greater than or equal 10% OR IgG greater than 3 g/dL or IgA greater than 2 g/dL or Bence Jones proteinuria greater than 1g/24h (but not both together) and always in the absence of lytic lesions, hypercalcemia, renal failure and anemia. These patients may be included in the study if they meet the following additional criteria: A percentage of phenotypically aberrant plasma cells (PCs) within the bone marrow (BM) PC compartment (aPC/ BM PC) greater than or equal 95% and immunoparesis, defined as a reduction in the levels of 1 or 2 immunoglobulin (Igs) of more than 25% compared with the normal values of the corresponding Ig.
- SMM at ultra high risk of progression to symptomatic disease:
a. Presence of more than 1 focal lesion in MRI (ideally whole body MRI).
b. Infiltration in the BM equal or higher than 60%.
c. Ratio of involved/uninvolved serum FLC higher than 100.
5.-The patient must have an ECOG performance status less than 2.
6.-The patient must be able to attend the scheduled visits.
7.-Women of childbearing potential must have a negative pregnancy test (serum or urine) within the 14 days before the starting the study drug. In addition, sexually active women must agree to use contraceptive methods (hormone contraceptives [oral, injectable or implanted], tubal ligation, intrauterine device, barrier contraceptives with spermicide or have a vasectomised partner) while receiving the study drug. Women of childbearing potential must agree to undergo pregnancy tests every 4 weeks while receiving the study drug (every 14 days for women with irregular menstrual cycles) and 4 weeks after the last dose of study drug.

1.- El paciente debe ser capaz de cumplir todos los requisitos del ensayo clínico, de acuerdo con el criterio del investigador.
2.- El paciente debe firmar voluntariamente el documento de consentimiento informado antes de que se lleve a cabo cualquiera de los procedimientos del estudio que no formen parte de la norma asistencial para estos pacientes, haciéndole saber que puede retirarse del estudio en cualquier momento, sin perjuicio del tratamiento que pueda recibir en el futuro.
3.- El paciente deberá tener más de 18 años y menos de 65 años, y ser candidato a recibir tratamiento a altas dosis y un trasplante autólogo de progenitores de sangre periférica.
4.- El paciente debe haber sido diagnosticado con mieloma múltiple asintomático de alto riesgo de progresar a mieloma sintomático, o de riesgo ultra alto de progresar a enfermedad sintomática. Esto es:
- Mieloma múltiple asintomático de alto riesgo de progresar a enfermedad sintomática:
a. Infiltrado de médula ósea con células plasmáticas ? 10% y presencia de un componente monoclonal, IgG >3 g/dl o IgA >2 g/dl o proteinuria de Bence Jones >1 g/24h y ausencia de lesiones líticas, hipercalcemia, insuficiencia renal (creatinina < 2 mg/dl) y anemia (hemoglobina > 10 g/dl o que no esté 2 g/dl por debajo del límite inferior de la normalidad).
b. Infiltrado de MO con CP ?10% O IgG >3 g/dl o IgA >2 g/dl o proteinuria de Bence Jones > 1 g/24 h (pero no ambos a la vez), y siempre en ausencia de lesiones líticas, hipercalcemia, insuficiencia renal y anemia. Estos pacientes podrán incluirse en el estudio si cumplen los siguientes criterios adicionales: Presencia de un porcentaje de células plasmáticas fenotípicamente anormales en el compartimento de células plasmáticas de la médula ósea (CPa/células plasmáticas) ? 95% e inmunoparesia, definida como una reducción de la concentración de 1 ó 2 inmunoglobulinas (Igs) de más del 25%, en comparación con los valores normales de la Ig correspondiente.
o Mieloma múltiple asintomático de riesgo ultra alto de progresar a enfermedad sintomática:
a. Presencia de más de 1 lesión focal en la RMN (idealmente, en una RMN de cuerpo entero).
b. Infiltrado en la médula ósea ? 60%.
c. Ratio de cadenas ligeras libres séricas implicadas / no implicadas mayor de 100.
5.- El paciente debe presentar una categoría funcional ECOG inferior a 2.
6.- El paciente debe ser capaz de acudir a las visitas programadas.
7.- Las mujeres en edad fértil deben presentar un resultado negativo en una prueba de embarazo (en suero u orina) que se realizará en el transcurso de los 14 días previos al inicio de la administración del fármaco del estudio.
Por otra parte, las mujeres sexualmente activas deben estar de acuerdo en utilizar métodos anticonceptivos (anticonceptivos hormonales [orales, inyectables o implantados], ligadura de trompas, dispositivo intrauterino, anticonceptivos de barrera con espermicida, o que la pareja se haya sometido a una vasectomía) mientras estén recibiendo el fármaco del estudio. Las mujeres en edad fértil deben estar de acuerdo en someterse a pruebas de embarazo cada 4 semanas mientras estén recibiendo el fármaco del estudio (cada 14 días, en el caso de aquellas mujeres que presenten ciclos menstruales irregulares) y 4 semanas después de la última dosis del fármaco del estudio.

E.4

Principal exclusion criteria

1.-Any physical condition or psychiatric disorder that would prevent the patient from signing or understanding the informed consent form.
2.-Previous treatment for smoldering multiple myeloma.
3.-Pregnancy or breastfeeding.
4.-Presence of lytic lesions, anemia, renal failure or hypercalcemia.
5.-Any of the following laboratory abnormalities:
-Absolute neutrophil count (ANC) less than 1,000/mm3
-Platelet count less than 75,000/mm3.
-Serum GOT or GPT greater than 3 x upper limit of normal
-Serum total bilirubin greater than 2 x upper limit of normal
6.-Prior history of neoplasm other than multiple myeloma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been disease-free for > 5 years.
7.-Major surgery within 4 weeks before inclusion in the study.
8.-Known active infection by human aquired immunodeficiency virus, B or C hepatitis virus.
9.-Any investigational drug within 30 days before inclusion in the study.
10.-Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrolment.
11.-Unstable angina or myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
12.-Uncontrolled hypertension or uncontrolled diabetes.
13.-Significant neuropathy (Grades 3?4, or Grade 2 with pain) within 14 days prior to enrollment.
14.-Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib).
15.-Contraindication to any of the required concomitant drugs or supportive treatments, including intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
16.-LVEF less than 40
17.-Pulmonary hypertension

1.- Cualquier condición física o trastorno psiquiátrico que podría impedir que el paciente firmara o comprendiera el documento de consentimiento informado.
2.- Haber recibido tratamiento previo para el mieloma múltiple asintomático.
3.- Pacientes embarazadas o en período de lactancia.
4.- Presencia de lesiones líticas, anemia, insuficiencia renal o hipercalcemia.
5.- Cualquiera de los siguientes valores analíticos anormales:
- Recuento absoluto de neutrófilos (RAN) inferior a 1.000/mm3.
- Recuento plaquetario inferior a 75.000/mm3.
- GOT o GPT séricas superior 3 veces el límite superior de la normalidad.
- Bilirrubina sérica total superior 2 veces el límite superior de la normalidad
6.- Antecedentes de neoplasias distintas al mieloma múltiple (excepto en el caso de los carcinomas de piel de células basales o células escamosas o el carcinoma in situ del cuello uterino o de mama), a menos que el paciente no haya presentado enfermedad durante > 5 años.
7.- Haberse sometido a una intervención de cirugía mayor en el transcurso de las 4 semanas previos a la inclusión en el estudio.
8.- Presencia de infección activa por el virus de inmunodeficiencia adquirida, el virus de la hepatitis B o C.
9.- Haber recibido cualquier fármaco en fase de investigación en el transcurso de las 4 semanas previas a la inclusión en el estudio.
10.- Presencia de una infección activa aguda que requiera tratamiento (antibióticos sistémicos, antivíricos o antifúngicos), en el transcurso de los 14 días previos al reclutamiento.
11.- Haber experimentado angina inestable o infarto de miocardio en el transcurso de los 6 meses previos al reclutamiento, insuficiencia cardiaca de clase III o IV (de acuerdo con los criterios de la New York Heart Association, angina sin controlar, antecedentes de arteriopatía coronaria intensa, arritmias ventriculares intensas sin controlar, síndrome de disfunción sinusal o indicios electrocardiográficos de isquemia aguda o alteraciones del sistema de conducción de grado 3, a menos que el paciente tenga un marcapasos.
12.- Hipertensión sin controlar o diabetes sin controlar.
13.- Neuropatía significativa (grados 3-4, o grado 2 con presencia de dolor), en el transcurso de los 14 días previos al reclutamiento.
14.- Antecedentes conocidos de alergia a captisol (un derivado de la ciclodextrina que se utiliza para solubilizar el carfilzomib).
15.- Presentar una contraindicación que impida administrar los fármacos concomitantes o tratamientos complementarios, incluida la intolerancia a la hidratación, debido a un deterioro pulmonar o cardiaco preexistente.
16.- FEVI inferior a 40
17.- Hipertensión pulmonar.

E.5 End points

E.5.1

Primary end point(s)

Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT

Tasa de respuestas completas inmunofenotípicas (RC por citometría de flujo) el día +100 después del tratamiento de inducción y HDT-ASCT.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day +100 after induction and HDT-ASCT

Día +100 después del tratamiento de inducción y HDT-ASCT

E.5.2

Secondary end point(s)

1.-Immunophenotypic complete remission rate (Flow-CR) after consolidation and at 3 and 5 years after HDT-ASCT.
2.-Response rates (sCR, CR, VGPR and OR) after the different parts of the treatment, induction, HDT-ASCT, consolidation and maintenance.
3.-TTP to symptomatic disease, PFS and OS.
4.-Safety profile of the induction, HDT-ASCT, consolidation and maintenance.

1.- Tasa de respuesta inmunofenotípica completa (RC - citometría de flujo), tras el tratamiento de consolidación, y a los 3 y 5 años tras el HDT-ASCT.
2.- Tasas de respuesta (RCe, RC, MBRP y tasa global de respuesta [ORR, por sus siglas en inglés] ) tras las diferentes partes del tratamiento (inducción, HDT-ASCT, consolidación y mantenimiento).
3.- a enfermedad sintomática, SLP y SG.
4.- Perfil de seguridad tras el tratamiento de inducción, trasplante, consolidación y el tratamiento de mantenimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

After induction, HDT-ASCT, consolidation and maintenance. And at 3 and 5 years after HDT-ASCT.

Tras las diferentes fases del tratamiento de inducción, HDT-ASCT, consolidación y mantenimiento, y 3 y 5 años tras el HDT-ASCT.

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)

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

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

Last patient last visit.

Última visita del último paciente en estudio.

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)

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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)

Expected normal treatment.

Práctica clínica habitual.

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

2015-03-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-13

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials