Clinical Trials Register

Summary
EudraCT Number:	2018-001741-14
Sponsor's Protocol Code Number:	TEM-MM-101
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:	2019-06-12
Trial results	View 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

2018-001741-14

A.3

Full title of the trial

A phase I/II dose escalation study evaluating safety and activity of autologous CD34+-enriched hematopoietic progenitor cells genetically modified with a lentiviral vector encoding for the human interferon-alfa2 gene in multiple myeloma patients with early relapse after intensive front line therapy

Sperimentazione clinica di fase I/II atta a valutare la sicurezza e l’attività di dosi crescenti di cellule staminali ematopoietiche autologhe CD34+ geneticamente modificate con un vettore lentivirale codificante per il gene umano dell’interferone-alfa2 in pazienti affetti da mieloma multiplo recidivato precocemente dopo trattamenti intensivi di prima linea

A.3.1

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

A clinical gene therapy study with hematopoietic stem cells for the treatment of patients suffering from a plasma cell tumor.

Studio clinico di terapia genica con cellule staminali ematopoietiche per il trattamento di pazienti affetti da un tumore delle plasmacellule

A.3.2

Name or abbreviated title of the trial where available

TEM-MM

A.4.1

Sponsor's protocol code number

TEM-MM-101

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	OSPEDALE SAN RAFFAELE
B.1.3.4	Country	Italy
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	Genenta Science S.r.l.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	OSPEDALE SAN RAFFAELE
B.5.2	Functional name of contact point	Ufficio Ricerche Cliniche – Stem Ce
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina, 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	02-26434289
B.5.5	Fax number	02-26434760
B.5.6	E-mail	urc.scp@hsr.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	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	Temferon
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Temferon
D.3.9.2	Current sponsor code	Temferon
D.3.9.3	Other descriptive name	HSPC autologhe geneticamente modificate con vettore lentivirale TIA126-LV, codificante per cDNA hIFN-2
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2500000 to 10000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	MYELOSTIM - 34 1 FLACONCINO LIOFILIZZATO 33.6 MIU + SIRINGA PRERIEMPITA SOLVENTE 1 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	CHUGAI SANOFI AVENTIS
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	LENOGRASTIM
D.3.2	Product code	LENOGRASTIM
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENOGRASTIM
D.3.9.2	Current sponsor code	LENOGRASTIM
D.3.9.3	Other descriptive name	LENOGRASTIM
D.3.10	Strength
D.3.10.1	Concentration unit	million IU million international units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	34
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	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	MOZOBIL - 20 MG/ML - SOLUZIONE INIETTABILE - USO SOTTOCUTANEO - FLACONCINO (VETRO) - 24 MG/1.2 ML 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	GENZYME 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/3/4/227
D.3 Description of the IMP
D.3.1	Product name	PLERIXAFOR
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PLERIXAFOR
D.3.9.2	Current sponsor code	PLERIXAFOR
D.3.9.3	Other descriptive name	PLERIXAFOR
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: 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	ENDOXAN BAXTER - 500 MG POLVERE PER SOLUZIONE INIETTABILE 1 FLACONE VETRO TIPO III 500 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER S.P.A.
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CICLOFOSFAMIDE
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CICLOFOSFAMIDE
D.3.9.2	Current sponsor code	CICLOFOSFAMIDE
D.3.9.3	Other descriptive name	CICLOFOSFAMIDE
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	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: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	REVLIMID - 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 LIMITED
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.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENALIDOMIDE
D.3.9.2	Current sponsor code	LENALIDOMIDE
D.3.9.3	Other descriptive name	LENALIDOMIDE
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: 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	VELCADE - 1 FLACONCINO DA 3.5 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BORTEZOMIB
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BORTEZOMIB
D.3.9.2	Current sponsor code	BORTEZOMIB
D.3.9.3	Other descriptive name	BORTEZOMIB
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.5
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: 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	SOLDESAM - 0.2% GOCCE ORALI, SOLUZIONE FLACONE 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	LABORATORIO FARMACOLOGICO MILANESE S.R.L.
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	DESAMETASONE
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
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	DESAMETASONE
D.3.9.3	Other descriptive name	DESAMETASONE
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
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: 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	ALKERAN - 50 MG/10 ML POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE 1 FLACONCINO POLVERE + 1 FLACONCINO SOLVENTE DA 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ASPEN PHARMA TRADING LIMITED
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/3/15/1463
D.3 Description of the IMP
D.3.1	Product name	MELFALAN
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MELFALAN
D.3.9.2	Current sponsor code	MELFALAN
D.3.9.3	Other descriptive name	MELFALAN
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	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: 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	ZARZIO - 30MU (60MU/ML) - SOLUZIONE INIETTABILE O PER INFUSIONE - USO SOTTOCUTANEO O ENDOVENOSO-SIRINGA PRERIEMPITA (VETRO) 0.5 ML 1 SIRINGA PRERIEMPITA
D.2.1.1.2	Name of the Marketing Authorisation holder	SANDOZ GMBH
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	FILGRASTIM
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FILGRASTIM
D.3.9.2	Current sponsor code	FILGRASTIM
D.3.9.3	Other descriptive name	FILGRASTIM
D.3.10	Strength
D.3.10.1	Concentration unit	Munit million units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Multiple myeloma in early relapse after intensive front line therapy

Mieloma multiplo recidivato precocemente dopo trattamenti intensivi di prima linea

E.1.1.1

Medical condition in easily understood language

Multiple myeloma in early relapse after intensive front line therapy

Mieloma multiplo recidivato precocemente dopo trattamenti intensivi di prima linea

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	20.0
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 evaluate safety and tolerability of escalating doses of Temferon in multiple myeloma patients with early relapse after intensive front line therapy.

Valutare la sicurezza e la tollerabilità di dosi crescenti di Temferon in pazienti con mieloma multiplo recidivato precocemente dopo terapia intensiva in prima linea.

E.2.2

Secondary objectives of the trial

To evaluate biological activity and efficacy of escalating doses of Temferon as maintenance/consolidation treatment in multiple myeloma patients with early relapse after intensive front line therapy.

Valutare l'attività biologica e l'efficacia di dosi crescenti di Temferon come trattamento di mantenimento/consolidamento in pazienti con mieloma multiplo recidivato precocemente dopo terapia intensiva in prima linea.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Multiple myeloma patients with early relapse after intensive front-line treatment and disease measurable by serum biomarkers that have obtained at least a VGPR after second-line salvage treatment;
2. Able and willing to provide written informed consent;
3. Able to comply with study protocol and procedures;
4. Male or Female;
5. Age 18-70 years;
6. Fit patients: Performance status scores: ECOG <2 and Karnofsky > 70%; Life expectancy of ≥ 6 months;
7. Adequate cardiac, renal, hepatic and pulmonary functions;
8. Women of child-bearing potential enrolled in the study must have a negative pregnancy test at screening and agree to use acceptable methods of contraception during the trial;
9. Men enrolled in the study with partners who are women of child bearing potential, must be willing to use an acceptable barrier contraceptive method during the trial or have undergone successful vasectomy at least 6 months prior to entry into the study.

1. Pazienti con mieloma multiplo recidivato precocemente dopo trattamento intensivo in prima linea, malattia misurabile mediante biomarcatori sierici e che hanno ottenuto una VGPR dopo un trattamento di salvataggio in seconda linea;
2. Pazienti in grado e disposti a fornire il consenso informato scritto;
3. Pazienti in grado di rispettare il protocollo di studio e le procedure;
4. Maschi e femmine;
5. Età 18-70 anni;
6. Pazienti in salute: ECOG < 2 e Karnofsky >70%, aspettativa di vita ≥ 6 mesi;
7. Adeguate funzioni cardiache, renali, epatiche e polmonari;
8. Le donne in età fertile arruolate nello studio devono sottoporsi a un test di gravidanza negativo allo screening e accettare di utilizzare metodi contraccettivi accettabili durante lo studio;
9. Gli uomini arruolati nello studio con partner che sono donne potenzialmente fertili, devono essere disposti a utilizzare un metodo contraccettivo di barriera accettabile durante lo studio o aver subito una vasectomia di successo almeno 6 mesi prima dell'ingresso nello studio.

E.4

Principal exclusion criteria

1. Use of other investigational agents within 4 weeks prior to experimental treatment (within 6 weeks if use of long-acting agents);
2. Severe active viral, bacterial, or fungal infection at eligibility evaluation;
3. Active autoimmune disease or a history of clinically relevant autoimmune manifestations requiring immunosuppressive treatment, i.e. psoriasis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, immune-mediated peripheral neuropathies;
4. Sarcoidosis requiring active steroid or immunosuppressive treatment;
5. Primary amyloidosis;
6. History of neuropsychiatric illness including severe depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia or suicidal tendency;
7. Neuropathy > grade 2;
8. History of severe cardiovascular disease such as prior stroke, coronary artery disease requiring intervention, unresolved arrhythmias;
9. Malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or family history of familial cancer syndromes;
10. Myelodysplasia, cytogenetic or molecular alterations specifically associated with clonal hematopoiesis of the myeloid lineage, or other serious hematological disorder other than the plasma cell dyscrasia;
11.Other clinical conditions judged by the Investigator non-compatible with the study procedures;
12. Positivity for HIV-1, HIV-2 (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection;
13. Active alcohol or substance abuse within 6 months of the study;
14. Pregnancy or lactation;
15. Previous allogeneic bone marrow transplantation, kidney or liver transplant, or gene therapy;
16. Prior to conditioning: inability to meet the target mobilization cell number after at least 2 attempts of HSPC collection.

1. Uso di altri agenti investigativi nelle 4 settimane precedenti il trattamento sperimentale (entro 6 settimane se si usano agenti a lunga durata d'azione);
2. Grave infezione virale, batterica o fungina attiva alla valutazione dell'idoneità;
3. Malattia autoimmune attiva o una storia rilevante di importanti manifestazioni autoimmuni, in particolare psoriasi, sarcoidosi, lupus eritematoso sistemico, artrite reumatoide, vasculite, neuropatie periferiche immuno-mediate;
4. Sarcoidosi che richiede trattamento attivo con steroidi o uso di agenti immunosuppressivi;
5. Amiloidosi primaria;
6. Storia di malattia neuropsichiatrica inclusa depressione, schizofrenia, disturbi bipolari, compromissione della funzione cognitiva, demenza o tendenza al suicidio;
7. Neuropatia> grado 2;
8. Anamnesi di gravi malattie cardiovascolari come un precedente ictus, malattia coronarica che richiede un intervento, aritmie non risolte;
9. Neoplasie maligne (eccetto il tumore cutaneo locale o neoplasia intraepiteliale cervicale) o storia familiare di sindromi da cancro familiare;
10. Mielodisplasia, alterazioni citogenetiche o molecolari specificatamente associate all'ematopoiesi clonale del lignaggio mieloide o altra grave patologia ematologica diversa dalla discrasia delle plasmacellule;
11. Altre condizioni cliniche giudicate dallo sperimentatore non compatibili con le procedure dello studio;
12. Positività per HIV-1, HIV-2 (sierologia o RNA) e/o HbsAg e/o HBV-DNA e/o HCV-RNA (o RNA HCV negativo ma con trattamento antivirale) e/o infezione da Treponema Pallidum o Mycoplasma;
13. Uso attivo o abuso di alcool o altre sostanze entro 6 mesi dallo studio;
14. Gravidanza o allattamento;
15. Precedente trapianto di midollo osseo allogenico, trapianto di rene o fegato o terapia genica;
16. Prima del condizionamento: incapacità, in seguito a mobilizzazione, di raggiungere il numero target di cellule HSPC dopo almeno 2 tentativi di raccolta.

E.5 End points

E.5.1

Primary end point(s)

- Engraftment of Temferon after reduced intensity conditioning (vector copy number [VCN] > 0.07 in myeloid cells between Day +30 and Day +100 in at least 2 patients);
- The proportion of patients achieving hematologic recovery by Day +30 from ASCT with non-manipulated autologous HSPC and infusion of Temferon;
- Safety of Temferon measured through the 24 months post Temferon infusion.

- Attecchimento di Temferon dopo regime di condizionamento a ridotta intensità (numero di copie vettore [VCN]> 0,07 nelle cellule mieloidi tra il giorno +30 e il giorno +100 in almeno 2 pazienti);
- Proporzione di pazienti che hanno ottenuto il recupero ematologico entro il giorno +30 dalla somministrazione di cellule staminali e progenitori (HSPC) autologhi non manipolati 5 e dall’infusione di Temferon.;
- Sicurezza di Temferon valutata nei 24 mesi successivi alla sua infusione.

E.5.1.1

Timepoint(s) of evaluation of this end point

Multiple timepoints up to 2 years

Multipli timepoints fino a 2 anni

E.5.2

Secondary end point(s)

- Presence of an IFN-alfa gene signature in the bone marrow (BM) of Temferon-treated patients.
- Presence of transduced myeloid cells in BM aspirate and peripheral blood (PB) at Day +30 and Day +100 post Temferon infusion as determined by VCN.
- Persistence of transduced myeloid cells in PB and BM as assessed by VCN for at least 12 weeks
- Overall response rate (ORR)
- Fraction of patients achieving complete response (CR) with minimal residual disease (MRD) levels ≤ 10-5 and 10-6 on BM aspirate
- Duration of maintenance of response during the 24 months post Temferon infusion
- Progression-free survival (PFS) and overall survival (OS) at 24 months post Temferon infusion.
- Change in health-related quality of life (HRQOL) at 6, 12 and 24 months post Temferon infusion compared to screening.
- Change over time in performance status scores (ECOG and Karnofsky) through 24 months post Temferon infusion.

- Induzione, nel midollo osseo (BM) dei pazienti trattati con Temferon di geni IFN-responsivi.
- Presenza di cellule mieloidi trasdotte nell'aspirato midollare (BM) e nel sangue periferico (PB) al giorno +30 e giorno +100 dopo l'infusione di Temferon.
- Persistenza di cellule mieloidi trasdotte in PB e BM valutata mediante VCN per almeno 12 settimane.
- Tasso di risposta obiettiva (ORR)
- Frazione di pazienti che raggiungono una risposta completa (CR) con malattia minima residua (MRD) ≤ 10-5 e 10-6 valutata su aspirato midollare.
- Durata del mantenimento della risposta nei 24 mesi successivi all'infusione di Temferon
- Sopravvivenza libera da progressione (PFS) e sopravvivenza globale (OS) a 24 mesi dall'infusione di Temferon.
- Cambiamento della qualità della vita correlata alla salute (HRQOL) a 6, 12 e 24 mesi dall'infusione di Temferon rispetto allo screening.

E.5.2.1

Timepoint(s) of evaluation of this end point

Multiple timepoints up to 2 years

Multipli timepoints fino a 2 anni

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

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

Yes

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

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

A dosi crescenti

Dose escalation

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

Number of subjects for this age range:

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Patients will be invited to participate in a long term follow-up study for an additional 6 years.

Al termine della sperimentazione, i pazienti saranno invitati a partecipare ad uno studio di follow-up a lungo termine di 6 anni.

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

2018-11-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-13

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

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