Clinical Trials Register

Summary
EudraCT Number:	2017-000555-10
Sponsor's Protocol Code Number:	HOVON147SMM/EMN15
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-08-23
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-000555-10

A.3

Full title of the trial

Carfilzomib, Lenalidomide and Dexamethasone versus Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma: A Randomized Phase II Study.

Carfilzomib, Lenalidomide e Desametasone versus Lenalidomide e Desametasone in pazienti affetti da Mieloma Multiplo Smoldering ad Alto Rischio: uno Studio Randomizzato di Fase II.

A.3.1

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

Carfilzomib, Lenalidomide and Dexamethasone versus Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma.

Carfilzomib, Lenalidomide e Desametasone versus Lenalidomide e Desametasone nel Mieloma Multiplo Smoldering ad Alto Rischio.

A.3.2

Name or abbreviated title of the trial where available

HOVON 147 SMM/ EMN15

A.4.1

Sponsor's protocol code number

HOVON147SMM/EMN15

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	HOVON
B.1.3.4	Country	Netherlands
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	HOVON Foundation
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	EMN Research Italy Impresa Sociale Srl
B.5.2	Functional name of contact point	Clinical Trial Office
B.5.3	Address:
B.5.3.1	Street Address	Via Nizza 52
B.5.3.2	Town/ city	Torino
B.5.3.3	Post code	10026
B.5.3.4	Country	Italy
B.5.4	Telephone number	0110243236
B.5.5	Fax number	0110133182
B.5.6	E-mail	amministrazione@emnresearch.it

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 - 15 MG CAPSULA RIGIDA - USO ORALE BLISTER (PCTFE/PVC/ALU) 21 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.2	Product code	[NA]
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.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 - 10 MG CAPSULA RIGIDA - USO ORALE BLISTER (PCTFE/PVC/ALU) 21 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.2	Product code	[NA]
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.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Dexamethasone 8 mg Tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Desametasone
D.3.2	Product code	[NA]
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	DESAMETASONE
D.3.9.2	Current sponsor code	NA
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 CAPSULA RIGIDA - USO ORALE BLISTER (PCTFE/PVC/ALU) 21 CASPULE
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.2	Product code	[NA]
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.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Dexamethasone 2mg Tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Macarthys Laboratories Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Desametasone
D.3.2	Product code	[NA]
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	DESAMETASONE
D.3.9.2	Current sponsor code	NA
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	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.2.1.1.1	Trade name	REVLIMID - 25 MG CAPSULA RIGIDA - USO ORALE BLISTER (PCTFE/PVC/ALU) 21 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.2	Product code	[NA]
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.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.2.1.1.1	Trade name	Dexamethasone 4 mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
D.2.1.2	Country which granted the Marketing Authorisation	Slovenia
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.3.2	Product code	[NA]
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	DESAMETASONE
D.3.9.2	Current sponsor code	NA
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	4
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.2.1.1.1	Trade name	KYPROLIS - 60 MG - POLVERE PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) - 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	AMGEN EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/548
D.3 Description of the IMP
D.3.1	Product name	Carfilzomib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carfilzomib
D.3.9.1	CAS number	868540-17-4
D.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 Multiplo Smoldering

E.1.1.1

Medical condition in easily understood language

Smoldering multiple myeloma

Mieloma Multiplo Smoldering

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10075894
E.1.2	Term	Smoldering 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

The primary objectives of the study are to: (a) to assess the progression-free survival rate of KRd versus Rd in patients with high-risk SMM.

Gli obiettivi primari dello studio sono: (a) valutare il tasso di sopravvivenza libera da progressione di KRd rispetto a Rd in pazienti con SMM ad alto rischio.

E.2.2

Secondary objectives of the trial

• To assess MRD status after 4 and 9 cycles induction treatment
• To assess the correlation between PFS and MRD
• To determine progression-free survival-2 (PFS2 )
• To determine duration of response (DOR)
• To determine overall survival (OS)
• To assess correlation of MRD status with PFS2, DOR and OS
• To evaluate toxicity of combination therapy (carfilzomib, lenalidomide, and dexamethasone)
• To evaluate disease heterogeneity in relation to clinical outcomes (molecular profiling on bone marrow samples)

• Valutare lo stato di MRD dopo 4 e 9 cicli di trattamento di induzione
• Valutare la correlazione tra PFS e MRD
• Determinare la sopravvivenza libera da progressione-2 (PFS2 )
• Determinare la durata della risposta (DOR)
• Determinare la sopravvivenza globale (OS)
• Valutare la correlazione dello stato di MRD con PFS2, DOR e OS
• Valutare la tossicità della terapia di combinazione (carfilzomib, lenalidomide e desametasone)
• Valutare l'eterogeneità della malattia in relazione agli esiti clinici (profilo molecolare su campioni di midollo osseo)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria:
- Serum M-protein =3 g/dl Or urinary monoclonal protein >500 mg per 24 hours And/or monoclonal bone marrow plasma cells =10-60 %
- Absence of CRAB symptoms and myeloma defining events.
• Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic and/or the PETHEMA criteria
• Measurable disease
• Age >18 years
• WHO/ECOG performance status <=2
• Patients must have normal organ and marrow function
• Calculated Creatinine Clearance = 50 ml/min
• Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to entry and again within 24 hours of starting lenalidomide treatment
• Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all pre-menopausal women) Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Plan
• Written informed consent
• Patient is capable of giving informed consent

• I pazienti devono avere un mieloma multiplo Smoldering confermato istologicamente o citologicamente in base ai criteri dell'International Myeloma Working Group 2014:
- Proteina M sierica =3 g/dl O proteine monoclonali urinarie >500 mg per 24 ore E/o plasmacellule monoclonali del midollo osseo =10-60%
- Assenza di sintomi CRAB e di eventi che definiscono il mieloma.
• I pazienti devono avere un mieloma multiplo Smoldering ad alto rischio basato sui criteri della Mayo Clinic e/o del PETHEMA
• Malattia misurabile
• Età >18 anni
• WHO/ECOG performance status <=2
• I pazienti devono avere una funzione d'organo e midollare normale
• Clearance della creatinina calcolata = 50 ml/min
• Le donne in età fertile devono avere un test di gravidanza negativo su siero o urina entro 10-14 giorni prima dell'ingresso e di nuovo entro 24 ore dall'inizio del trattamento con lenalidomide
• Le pazienti devono essere disposte e capaci di usare un'adeguata contraccezione durante e dopo la terapia (tutti gli uomini, tutte le donne in pre-menopausa) Le pazienti devono essere in grado di aderire ai requisiti del piano di prevenzione della gravidanza con lenalidomide
• Consenso informato scritto
• La paziente è in grado di dare il consenso informato

E.4

Principal exclusion criteria

• Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)
• Amyloid Light-chain (AL) amyloidosis
• Patients who are receiving any other investigational agents
• Concurrent systemic treatment or prior therapy within 4 weeks for SMM
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
• History of allergic reactions attributed to immunomodulatory agents and proteasome inhibitors
• Uncontrolled hypertension or diabetes
• Pregnant or lactating females.
• Significant cardiovascular disease with NYHA grade III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
• Active hepatitis B or C infection
• Known or suspected HIV infection
• Incidence of gastrointestinal disease that would prevent absorption
• Significant neuropathy =Grade 3 or grade 2 with pain within 14 days of enrollment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection
• History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years
• Major surgery within 1 month prior to enrollment
• Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

• Pazienti con mieloma multiplo sintomatico (cioè con eventi che definiscono il mieloma)
• Amiloidosi a catena leggera (AL)
• Pazienti che stanno ricevendo qualsiasi altro farmaco sperimentale
• Trattamento sistemico concomitante o terapia precedente entro 4 settimane per il SMM
• Controindicazione a qualsiasi farmaco concomitante, compresi gli antivirali, la profilassi dell'anticoagulazione, la profilassi della lisi tumorale o l'idratazione data prima della terapia
• Storia di reazioni allergiche attribuite ad agenti immunomodulatori e inibitori del proteasoma
• Ipertensione o diabete non controllati
• Pazienti donne incinte o in allattamento
• Malattia cardiovascolare significativa con sintomi NYHA di grado III o IV, o cardiomegalia ipertrofica, o cardiomegalia restrittiva, o infarto del miocardio entro 3 mesi prima dell'arruolamento, o angina instabile, o aritmia instabile
• Infezione attiva da epatite B o C
• Infezione da HIV nota o sospetta
• Incidenza di malattie gastrointestinali che impedirebbero l'assorbimento
• Neuropatia significativa =grado 3 o grado 2 con dolore entro 14 giorni dall'arruolamento
• Malattie intercorrenti non controllate, incluse, ma non limitate a, infezioni in corso o attive
• Anamnesi di altri tumori maligni (a parte il carcinoma basocellulare della pelle o il carcinoma in situ della cervice uterina) tranne se il paziente è stato libero da sintomi e senza terapia attiva per almeno 5 anni
• Operazione chirurgica maggiore entro 1 mese prima dell'arruolamento
• Preesistente compromissione polmonare, cardiaca o renale che impedisca misure di idratazione
• Qualsiasi condizione psicologica, familiare, sociologica e geografica che possa ostacolare la conformità al protocollo dello studio e al programma di follow-up

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival rate, defined as time from study entry to progression or death, whichever comes first

Tasso di sopravvivenza libera da progressione, definito come il tempo trascorso dall'ingresso nello studio alla progressione o alla morte, a seconda di quale evento si verifichi per primo

E.5.1.1

Timepoint(s) of evaluation of this end point

The endpoints will be evaluated when data of all patients are available

L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti

E.5.2

Secondary end point(s)

Duration of response (DOR), defined as time from response to progression or death, whichever comes first; MRD status after induction cycle 4 and 9; Progression-free survival-2 (PFS2), defined at time from randomization to progression after second-line treatment or death, whichever comes first; Overall survival (OS), defined as time from study entry to death from any cause. Patients still alive at the date last contact will be censored; Correlation of MRD status with PFS, PFS2, DOR and OS; Toxicity of combination therapy (carfilzomib, lenalidomide, and dexamethasone)

Durata della risposta (DOR), definita come il tempo dalla risposta alla progressione o al decesso, a seconda di ciò che accade prima; Stato MRD dopo il ciclo di induzione 4 e 9; Sopravvivenza libera da progressione-2 (PFS2), definita dal tempo che intercorre tra la randomizzazione e la progressione dopo il trattamento di seconda linea o il decesso, a seconda di quale evento si verifichi per primo; Sopravvivenza globale (OS), definita come tempo dall'ingresso nello studio alla morte per qualsiasi causa. I pazienti ancora vivi alla data dell'ultimo contatto saranno censurati; Correlazione dello stato MRD con PFS, PFS2, DOR e OS; Tossicità della terapia combinata (carfilzomib, lenalidomide e desametasone)

E.5.2.1

Timepoint(s) of evaluation of this end point

The endpoints will be evaluated when data of all patients are available; The endpoints will be evaluated when data of all patients are available; The endpoints will be evaluated when data of all patients are available; The endpoints will be evaluated when data of all patients are available; The endpoints will be evaluated when data of all patients are available; The endpoints will be evaluated when data of all patients are available

L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti; L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti; L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti; L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti; L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti; L'endpoint sarà valutato quando saranno disponibili i dati di tutti i pazienti

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)

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

Italy

Netherlands

Norway

Czechia

Greece

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

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

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

120

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)

According to local guidelines

Secondo le linee guida locali

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	HOVON Foundation
G.4.3.4	Network Country	Netherlands

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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