Clinical Trials Register

Summary
EudraCT Number:	2018-004767-31
Sponsor's Protocol Code Number:	CC-92480-MM-002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-22
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-004767-31

A.3

Full title of the trial

A Phase 1/2, Multicenter, Open-label, Study to Determine the Recommended Dose and Regimen, and Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination with Standard Treatments in Subjects with Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)

Studio di fase 1/2, multicentrico, in aperto per determinare la dose raccomandata e il regime di trattamento e valutare la sicurezza e l’efficacia preliminare di CC-92480 somministrato in combinazione con le terapie standard in soggetti con Mieloma Multiplo recidivante o refrattario (RRMM) e con Mieloma Multiplo di nuova diagnosi (NDMM).

A.3.1

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

A Trial to Determine the Recommended Dose, Dosing Pattern, Effectiveness and Safety of CC-92480 When Combined with Standard Treatments in Patients Who have Non-responsive or Recurrent Myeloma and in Patients Who Have Been Newly Diagnosed with Myeloma.

Studio per determinare dose raccomandata, schema di dosaggio, efficacia e sicurezza di CC-92480 combinato con i trattamenti standard in pazienti affetti da mieloma recidivante o non responsivo e in pazienti con nuova diagnosi di mieloma.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CC-92480-MM-002

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	CELGENE CORPORATION
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Celgene Corporation
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	Celgene Corporation
B.5.2	Functional name of contact point	ClinicalTrialDisclosure
B.5.3	Address:
B.5.3.1	Street Address	9225 Indian Creek Parkway, Suite 900
B.5.3.2	Town/ city	Overland Park, Kansas
B.5.3.3	Post code	66210
B.5.3.4	Country	United States
B.5.4	Telephone number	+18882601599
B.5.5	Fax number	+19132660394
B.5.6	E-mail	ClinicalTrialDisclosure@celgene.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	Desametasone 20 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Centrafarm B.V.
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	[-]
D.3.4	Pharmaceutical form	Solution for 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	DESAMETASONE
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB36974
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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	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	CC-92480 0.1 mg
D.3.2	Product code	[CC-92480]
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	Agente modificante di cereblon (CM) [Cereblon-modifying (CM) agent]
D.3.9.1	CAS number	2259648-80-9
D.3.9.2	Current sponsor code	CC-92480
D.3.9.4	EV Substance Code	SUB190554
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	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	CC-92480 0.5 mg
D.3.2	Product code	[CC-92480]
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	Agente modificante di cereblon (CM) [Cereblon-modifying (CM) agent]
D.3.9.1	CAS number	2259648-80-9
D.3.9.2	Current sponsor code	CC-92480
D.3.9.4	EV Substance Code	SUB190554
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	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	CC-92480 2 mg
D.3.2	Product code	[CC-92480]
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	Agente modificante di cereblon (CM) [Cereblon-modifying (CM) agent]
D.3.9.1	CAS number	2259648-80-9
D.3.9.2	Current sponsor code	CC-92480
D.3.9.4	EV Substance Code	SUB190554
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: 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	VELCADE 3,5 mg polvere per soluzione iniettabile
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	-
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BORTEZOMIB
D.3.9.1	CAS number	179324-69-7
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB20020
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3500
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	DARZALEX 20 mg/ml concentrato per soluzione per infusione.
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1153
D.3 Description of the IMP
D.3.1	Product name	DARZALEX 20 mg/ml concentrato per soluzione per infusione.
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Concentrate for solution for 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	DARATUMUMAB
D.3.9.1	CAS number	945721-28-8
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB175772
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo monoclonale umanizzato
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	Kyplrolis 60 mg polvere per soluzione per infusione
D.2.1.1.2	Name of the Marketing Authorisation holder	EU/1/15/1060/001 (EU Marketing Authorisation)
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/548
D.3 Description of the IMP
D.3.1	Product name	carfilzomib
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Powder for solution for 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	-
D.3.9.4	EV Substance Code	SUB32911
D.3.10	Strength
D.3.10.1	Concentration unit	g/ml gram(s)/millilitre
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.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	Desametasone 2 mg compresse
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	[-]
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	-
D.3.9.4	EV Substance Code	SUB36974
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: 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.2.1.1.1	Trade name	Desametasone-ratiopharm compresse 4 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	ratiopharm GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	[-]
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	-
D.3.9.4	EV Substance Code	SUB36974
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.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

Relapsed or refractory multiple myeloma (RRMM) and newly diagnosed MM (NDMM)

Mieloma multiplo recidivante o refrattario (RRMM) o MM di nuova diagnosi (NDMM)

E.1.1.1

Medical condition in easily understood language

Newly diagnosed multiple myeloma and multiple myeloma that recurs or is resistant to other treatments previously tried by the patient.

Mieloma multiplo di nuova diagnosi o mieloma multiplo recidivante o resistente ad altri trattamenti precedentemente provati dal paziente.

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	21.0
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.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the recommended dose and regimen, and evaluate the safety and preliminary efficacy of CC-92480 in combination with standard treatments in subjects with RRMM and NDMM.

Determinare la dose e il regime raccomandati e valutare la sicurezza e l’efficacia preliminare di CC-92480 in combinazione con i trattamenti standard in soggetti con RRMM e NDMM.

E.2.2

Secondary objectives of the trial

Evaluate additional measures of efficacy (time-to-response, duration of response, complete response rate) of CC-92480 in combination with standard treatments in subjects with RRMM and NDMM.

Valutare ulteriori misure di efficacia (tempo di risposta, durata della risposta, tasso di risposta completa) di CC-92480 in combinazione con i trattamenti standard in soggetti con RRMM e NDMM.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is = 18 years of age at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
5. Females of childbearing potential (FCBP) must:
a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two reliable forms of contraception as defined in the Pregnancy Prevention Plan (PPP)without interruption, 28 days prior to starting CC-92480, during the study treatment (including during dose interruptions), and for 28 days after the last dose of CC-92480 or 90 days after the last dose of BTZ (for Cohorts A, D and G) or DARA (for Cohorts B and E) or 6 months after the last dose of CFZ (for Cohorts C and F), whichever is later.
Note: A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point and, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.
6. Male subjects must:
a. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use of a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study (even during dose interruptions) and for at least 3 months following study treatment discontinuation, even if he has undergone a successful vasectomy.
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and coitus interruptus (withdrawal) are not acceptable methods of contraception.
7. Males must agree to refrain from donating sperm or semen while on study treatment, and for at least 3 months following last dose of study treatment. Females must refrain from egg cell (ova) donation while on study treatment, and for 28 days after the last dose of CC-92480.
8. All subjects must agree to refrain from donating blood while on study treatment and for 28 days after the last dose of study treatment.
9. All male and female subjects must follow all requirements defined in the Pregnancy Prevention Plan for Subjects in Clinical Trials.
Please refer to protocol for additional inclusion criteria for subjects in Cohorts A, B, C, D, E and F and for subjects in Cohort G.

1. Il soggetto ha = 18 anni di età al momento della firma del Modulo di consenso informato (IFC).
2. Il soggetto deve capire e firmare volontariamente un Modulo di consenso informato [ICF] prima che siano condotte valutazioni/procedure connesse allo studio.
3. Il soggetto è disposto e in grado di aderire al piano di visite dello studio e ad altri requisiti del protocollo.
4. Il soggetto presenta un punteggio del performance status dell’Eastern Cooperative Oncology Group (ECOG) di 0, 1 o 2.
5. Le donne in età fertile (‘Females of childbearing potential’, FCBP) devono:
a. Presentare 2 test di gravidanza negativi verificati dallo Sperimentatore prima di iniziare la terapia in studio. Acconsentire a sottoporsi a test di gravidanza continui durante il corso dello studio e dopo la fine del trattamento in studio. Questo si applica anche se il soggetto pratica completa astinenza* da contatti eterosessuali.
b. Impegnarsi a praticare astinenza completa* da contatti eterosessuali (che deve essere rivista ogni mese e documentata alla fonte) o acconsentire di usare almeno due metodi contraccettivi efficaci come definito nel Piano di prevenzione gravidanze (PPP) senza interruzione, 28 giorni prima di iniziare CC-92480, durante il trattamento in studio (comprese le interruzioni di dose) e per 28 giorni dopo l’ultima dose di CC-92480 o 90 giorni dopo l’ultima dose di BTZ (per le coorti A, D e G) o DARA (per le coorti B ed E) oppure 6 mesi dopo l’ultima dose di CFZ (per le coorti C e F), a seconda dell’evento che si verifica dopo.
Nota: Una donna in età fertile (FCBP) è una donna che: 1) ha avuto il menarca in qualsiasi momento e, 2) non si è sottoposta a isterectomia o ooforectomia bilaterale, o 3) non è entrata naturalmente in menopausa (l’amenorrea dovuta alla terapia anti-tumorale non esclude la possibilità di avere figli) da almeno 24 mesi consecutivi.
6. I soggetti di sesso maschile devono:
a. Praticare completa astinenza (che deve essere valutata su base mensile) o acconsentire ad usare un preservativo durante il contatto sessuale con una donna in stato di gravidanza o con una donna in età fertile mentre partecipano allo studio (anche durante le interruzioni di dose) e per almeno 3 mesi a seguito dell'interruzione del trattamento in studio, anche se il soggetto fosse stato sottoposto ad un intervento riuscito di vasectomia.
* L’astinenza completa è accettabile quando è conforme allo stile di vita preferito e abituale del soggetto. Astinenza periodica (es.: metodi a calendario, di ovulazione, sintotermici, post-ovulazione) e coito interrotto non sono metodi di contraccezione accettabili.
7. I soggetti di sesso maschile devono acconsentire di astenersi dal donare sperma o seme durante il trattamento in studio e per almeno 3 mesi dopo l’ultima dose del trattamento in studio. I soggetti di sesso femminile devono astenersi dal donare cellule uovo (ovuli) durante il trattamento in studio e per almeno 28 giorni dopo l’ultima dose di CC-92480.
8. Tutti i soggetti devono astenersi dal donare sangue durante il trattamento in studio e per almeno 28 giorni dopo l’ultima dose del trattamento in studio.
9. Tutti i soggetti di sesso maschile e femminile devono osservare tutti i requisiti definiti nel Piano di prevenzione gravidanze per i soggetti partecipanti agli studi clinici.

Fare riferimento al protocollo per gli ulteriori criteri di inclusione per i soggetti nelle coorti A, B, C, D, E e F e per i soggetti nella coorte G.

E.4

Principal exclusion criteria

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subject has any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) < 1,000/µL (for Phase 1 without growth factor support for = 7 days [= 14 days for pegfilgrastim])
b. Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to reach this level)
c. Hemoglobin < 8 g/dL (< 4.9 mmol/L)
d. Creatinine clearance (CrCl) < 45 mL/min (<30 mL/min for Cohort G)
e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
g. Serum total bilirubin > 1.5 x ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
h. Prothrombin time (PT)/international normalized ration (INR) > 1.5 x ULN or partial thromboplastin time (PTT) > 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
5. Subject has peripheral neuropathy = Grade 2
6. Subject with gastrointestinal disease that may significantly alter the absorption of CC-92480.
7. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for = 5 years with the exception of the following non-invasive malignancies:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer or prostate cancer that is curative
8. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant amyloidosis.
9. Subject with known central nervous system (CNS) involvement with myeloma.
10. Subject has received immunosuppressive medication within the last 14 days of initiating study treatment. Please refer to protocol for exceptions to this criterion.

Please refer to protocol for exclusion criteria 11-19 and for additional exclusion criteria for subjects in Cohorts A, B, C, D, E and F and for subjects in Cohort G.

1. Il soggetto presenta una qualsiasi patologia medica significativa, anomalia di test di laboratorio,
o malattia psichiatrica che gli/le impedirebbe di partecipare allo studio.
2. Il soggetto presenta qualsiasi condizione, compresa la presenza di anomalie dei test di laboratorio, che lo/la esporrebbe a un rischio inaccettabile nel caso in cui partecipasse allo studio.
3. Il soggetto presenta qualsiasi condizione che confonde la capacità di interpretare i dati provenienti dallo studio.
4. Il soggetto presenta una qualunque delle seguenti alterazioni dei test di laboratorio:
a. Conta assoluta dei neutrofili (ANC) < 1.000/µL (per la Fase 1 senza supporto del fattore di crescita per = 7 giorni [= 14 giorni per pegfilgrastim])
b. Conta piastrinica: < 75.000/µL (non è ammissibile la trasfusione di un soggetto per raggiungere questo livello)
c. Emoglobina < 8 g/dL (< 4,9 mmol/L)
d. Clearance della creatinina (CrCl) < 45 mL/min (<30 mL/min per la Coorte G)
e. Calcio sierico corretto >13,5 mg/dL (>3,4 mmol/L)
f. Concentrazioni sieriche di aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) > 2,5 x ULN
g. Bilirubina totale sierica > 1,5 x ULN o > 3,0 mg/dL per soggetti con documentata sindrome di Gilbert
h. Tempo di protrombina (PT)/rapporto normalizzato internazionale (INR) > 1,5 x ULN o tempo di tromboplastina parziale (PTT) > 1,5 x ULN, (per soggetti che non ricevono terapia di anticoagulazione).
5. Il soggetto presente neuropatia periferica = Grado 2
6. Soggetto con malattia gastrointestinale che potrebbe alterare significativamente l’assorbimento di CC-92480.
7. Il soggetto presenta anamnesi precedente di neoplasie maligne, diverse da MM, a meno che il soggetto sia libero/a da malattia da = 5 anni, ad eccezione delle seguenti neoplasie maligne non invasive:
• Carcinoma cutaneo basocellulare
• Carcinoma cutaneo a cellule squamose
• Carcinoma in situ della cervice
• Carcinoma in situ della mammella
• Rilevamento istologico incidentale del cancro della prostata o cancro della prostata che sia curativo
8. Il soggetto presenta leucemia plasmacellulare, macroglobulinemia di Waldenstrom, sindrome POEMS (polineuropatia, organomegalia, endocrinopatia, proteine monoclonali e cambiamenti cutanei) o amiloidosi clinicamente significativa.
9. Soggetto con coinvolgimento noto del mieloma nel sistema nervoso centrale (CNS).
10. Il soggetto ha ricevuto farmaci immunosoppressivi entro gli ultimi 14 giorni dall’inizio del trattamento in studio. Fare riferimento al protocollo per le eccezioni a questo criterio.

Fare riferimento al protocollo per i criteri di esclusione 11-19 e per gli ulteriori criteri di esclusione per i soggetti nelle coorti A, B, C, D, E e F e per i soggetti nella coorte G.

E.5 End points

E.5.1

Primary end point(s)

Recommend Dose and Regimen
Review of dose-limiting toxicities (DLTs), safety, and if applicable, pharmacokinetics (PK), pharlmacodynamics (Pd), and/or preliminary efficacy data by the Safety Review Committee (SRC)

Safety
Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment

Overall response rate (ORR)
Best response = partial response (PR), according to the International Myeloma Working Group (IMWG) Uniform Response Criteria

Dose e regime raccomandati
Revisione delle tossicità dose-limitanti (DLT), della sicurezza e, se applicabile, della farmacocinetica (PK), della farmacodinamica (Pd) e/o dei dati preliminari sull’efficacia da parte del Comitato di Revisione della Sicurezza (SRC)

Sicurezza
Tipo, frequenza, serietà e gravità degli eventi avversi (AE), e il rapporto tra gli AE e trattamento in studio

Tasso di risposta complessivo (ORR)
Risposta migliore = risposta parziale (PR), secondo i Criteri di risposta uniformi del Gruppo di lavoro internazionale sul mieloma (International Myeloma Working Group, IMWG)

E.5.1.1

Timepoint(s) of evaluation of this end point

Recommend Dose and Regimen
Phase I

Safety
From first subject first visit until 28 days after the last subject discontinues study treatment.

Overall response rate (ORR)
From first subject enrollment until the last subject is no longer evaluable for response or has progressed.

Dose e regime raccomandati
Fase I

Sicurezza
Dalla prima visita del primo soggetto fino a 28 giorni dopo che l’ultimo soggetto interrompe il trattamento in studio.

Tasso di risposta complessivo (ORR)
Dall’arruolamento del primo soggetto finché l’ultimo soggetto non è più valutabile per la risposta o presenta progressione della malattia.

E.5.2

Secondary end point(s)

Time-to-response (TTR)
Time from first dose to the first documentation of response (PR or greater)

Duration of response (DOR)
Time from the first documentation of response (PR or greater) to the first documentation of progressive disease (PD) or death

Complete Response (CR) rate
Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria

Very good partial response (VGPR) rate (Cohorts D and E)
Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria

Tempo di risposta (TTR)
Tempo dalla prima dose alla prima documentazione di risposta (PR o superiore)

Durata della risposta (DOR)
Tempo dalla prima documentazione di risposta (PR o superiore) alla prima documentazione di malattia progressiva (PD) o decesso

Tasso di risposta completa (CR)
Percentuale di soggetti che hanno raggiunto CR o migliore secondo i Criteri uniformi di risposta dell’IMWG

Tasso di risposta parziale molto buona (VGPR) (coorti D ed E)
Percentuale di soggetti che hanno raggiunto VGPR o migliore secondo i Criteri uniformi di risposta dell’IMWG

E.5.2.1

Timepoint(s) of evaluation of this end point

From first subject enrollment until the last subject is no longer evaluable for response or has progressed.

Dall’arruolamento del primo soggetto finché l’ultimo soggetto non è più valutabile per la risposta o presenta progressione della malattia.

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose finding for Phase 2 portion of study

Determinazione della dose per la parte di Fase 2 dello studio

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

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.8.2.4

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

Canada

United States

Czechia

Denmark

France

Germany

Greece

Italy

Spain

E.8.7

Trial has a data monitoring committee

E.8.8

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

The End of Trial is defined as either the date of the last visit of the last subject to complete the post-treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date.

La Fine dello studio è definita come la data dell’ultima visita dell’ultimo soggetto che completa il follow-up post-trattamento, oppure la data di ricevimento dell’ultimo punto dati dell’ultimo soggetto, richiesto per l’analisi primaria, secondaria e/o esplorativa, come predefinito nel protocollo, qualunque sia la data che si verifica più tardi.

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:

143

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

155

F.4.2.2

In the whole clinical trial

238

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Nessuno

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

2019-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-23

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

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