Clinical Trials Register

Summary
EudraCT Number:	2013-001065-17
Sponsor's Protocol Code Number:	GEL-R-COMP-2013
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-06-10
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

Spain - AEMPS

A.2

EudraCT number

2013-001065-17

A.3

Full title of the trial

Phase II, randomised, multicentre study with two treatment arms (R-COMP versus R-CHOP) in newly diagnosed elderly patients (?60 years) with non-localised diffuse large B-cell lymphoma (DLBCL)/follicular lymphoma grade IIIb.

Estudio fase II aleatorizado y multicéntrico de dos brazos de tratamiento (R-COMP versus R-CHOP) en pacientes de edad avanzada (?60años) con linfoma difuso de células B grandes (LDCBG)/linfoma folicular grado IIIb no localizado de nuevo diagnóstico

A.3.1

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

Clinical trial to evaluate R-COMP versus R-CHOP in newly diagnosed patients with non-localised diffuse large B-cell lymphoma (DLBCL)/follicular lymphoma grade IIIb.

Ensayo clínico para comparar R-COMP frente a R-CHOP en pacientes con linfoma difuso de células B grandes (LDCBG)/linfoma folicular grado IIIb no localizado de nuevo diagnóstico

A.4.1

Sponsor's protocol code number

GEL-R-COMP-2013

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	Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GEL/TAMO)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Laboratorios TEVA
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dynamic Solutions
B.5.2	Functional name of contact point	Ángel Pérez
B.5.3	Address:
B.5.3.1	Street Address	C/Sant Antonio María Claret, 434
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08027
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34933511615
B.5.5	Fax number	+34933496341
B.5.6	E-mail	a.perez@dynasolutions.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Myocet 50 mg polvo y premezclas concentrado para dispersión liposómica para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	Cephalon Europe
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate for dispersion 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	DOXORUBICIN
D.3.9.1	CAS number	23214-92-8
D.3.9.4	EV Substance Code	SUB06391MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Doxorubicina
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare, S.L.U; Actavis Group Ptc Ehf;Tedec Meiji Farma, S.A.;Teva Pharma S.L.U.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate and solvent 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	DOXORUBICIN
D.3.9.1	CAS number	23214-92-8
D.3.9.4	EV Substance Code	SUB06391MIG
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	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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	MABTHERA 500 mg CONCENTRADO PARA SOLUCION PARA PERFUSION
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate and solvent for 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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.4	EV Substance Code	SUB12570MIG
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	10
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vincristina
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer, S.L.; Teva Genericos Española, S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	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	VINCRISTINE
D.3.9.1	CAS number	57-22-7
D.3.9.4	EV Substance Code	SUB00059MIG
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	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Prednisone
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck S.L.; Laboratorios Cinfa, S.A;Kern Pharma, S.L.; Pensa Pharma, S.A.U
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	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	PREDNISONE ACETATE
D.3.9.1	CAS number	125-10-0
D.3.9.4	EV Substance Code	SUB04024MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2.5 to 50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.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	Cyclophosphamide
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER ONCOLOGY, GMBH
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CYCLOPHOSPHAMIDE
D.3.9.1	CAS number	6055-19-2
D.3.9.3	Other descriptive name	CYCLOPHOSPHAMIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB16414MIG
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	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 7
D.1.2 and D.1.3	IMP Role	Comparator
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	MABTHERA 500 mg CONCENTRADO PARA SOLUCIÓN PARA PERFUSIÓN
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate and solvent 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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.4	EV Substance Code	SUB12570MIG
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	10
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 8
D.1.2 and D.1.3	IMP Role	Comparator
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	Vincristina
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer, S.L.; Teva Genericos
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	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	VINCRISTINE
D.3.9.1	CAS number	57-22-7
D.3.9.4	EV Substance Code	SUB00059MIG
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	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 9
D.1.2 and D.1.3	IMP Role	Comparator
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	Prednisone
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck S.L.; Laboratorios Cinfa,
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	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	PREDNISONE ACETATE
D.3.9.1	CAS number	125-10-0
D.3.9.4	EV Substance Code	SUB04024MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2.5 to 50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 10
D.1.2 and D.1.3	IMP Role	Comparator
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	Cyclophosphamide
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER ONCOLOGY, GMBH
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CYCLOPHOSPHAMIDE
D.3.9.1	CAS number	6055-19-2
D.3.9.3	Other descriptive name	CYCLOPHOSPHAMIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB16414MIG
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	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-localised diffuse large B-cell lymphoma/Follicular lymphoma grade IIIb

Linfoma difuso de células B grandes (LDCBG)/linfoma folicular grado IIIb no localizado

E.1.1.1

Medical condition in easily understood language

Non hodgkin lymphoma

Linfoma no Hodgkin

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

?To assess reduced of subclinical cardiotoxicity, determined by differences in LVEF, which involves the incorporation of non-pegylated liposomal doxorubicin (Myocet®) when replacing conventional doxorubicin in the standard R-CHOP regimen (R-COMP) to treat newly diagnosed elderly patients with non-localised DLBCL/follicular lymohoma grade IIIb

Evaluar la disminución de la toxicidad cardiaca subclínica, determinada en base a las diferencias en la fracción de eyección del ventrículo izquierdo (FEVI), que supone la incorporación de doxorubicina liposomal no pegilada (Myocet®) cuando sustituye a la doxorubicina convencional en la pauta R-CHOP (R-COMP) en el tratamiento de los pacientes de edad avanzada con LDCBG/linfoma folicular de grado IIIB de nuevo diagnóstico

E.2.2

Secondary objectives of the trial

? To assess event-free survival, progresion free survival and overall survival at 2 and 5 years after the end of the study treatment in both treatment arms.
? To determine the overall response rate and complete remissions in patients treated with R-CHOP and R-COMP.
? To assess clinical cardiovascular events according to the CTC criteria (version 4.0) of the NCI in both patient groups.
? To determine non-cardiac toxicity according to the CTC criteria (version 4.0) of the NCI in both patient groups.
? To determine and compare the values of troponin, NT-proBNP and LVEF, and establish their correlation with clinical and subclinical cardiotoxicity in both treatment arms.

? Evaluar la supervivencia libre de evento, supervivencia libre de progresión y la supervivencia global a los 2 años y a los 5 años tras la finalización del tratamiento en los dos brazos del estudio.
? Determinar la tasa de respuesta global y las remisiones completas en los pacientes tratados con R-CHOP y R-COMP.
? Evaluar la aparición de eventos cardiovasculares clínicos, según los criterios de terminología común para acontecimientos adversos del National Cancer Institute (NCI-CTCAE) (versión 4.0) en ambos grupos de pacientes.
? Determinar la toxicidad no cardiaca según los criterios NCI-CTCAE (versión 4.0) en ambos grupos de pacientes.
? Determinar y comparar los valores de troponina, NT-proBNP y FEVI, y establecer su relación con la cardiotoxicidad clínica y subclínica en ambas ramas de tratamiento.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Biological sub-study of GEL-R-COMP-2013 clinical trial
Flow cytometry sub-study of GEL-R-COMP-2013 clinical trial: bone marrow infiltration study by multi-parametric flow citometry and monitorization of minimal residual disease after treatment of patients with non-localised diffuse large B-cell lymphoma/Follicular lymphoma grade IIIB.
Pharmacokinetic sub-study of GEL-R-COMP-2031 clinical trial: population pharmacokinetic caracterization of conventional doxorubicin and Myocet after the adminisitration as part of R-CHOP and R-COMP in patients with non-localised diffuse large B-cell lymphoma/Follicular lymphoma grade IIIB.
Pharmacogenomic sub-study of GEL-R-COMP-2013 clinical trial: determining of resistances and adverse events to drugs by the analysis of genes related to absortion, transportation, metabolism and excretion of drugs.

Subestudio biológico del ensayo clínico GEL-R-COMP-2013.
Subestudio de citometría de flujo del ensayo clínico GEL-R-COMP-2013: estudio de la infiltración de la médula ósea mediante citometría de flujo multiparamétrica y monitorización de enfermedad mínima residual tras tratamiento de pacientes con linfoma difuso de células B grandes/linfoma folicular grado IIIB.
Subestudio farmacocinético del ensayo clínico GEL-R-COMP-2013: caracterización farmacocinética poblacional de doxorubicina convencional y doxorubicina liposomal no pegilada (Myocet®) tras su administración como parte de las pautas de tratamiento R-COMP y R-CHOP en el linfoma difuso de células B grandes/linfoma folicular grado IIIB de nuevo diagnóstico en pacientes de edad avanzada.
? Subestudio farmacogenómico del ensayo clínico GEL-R-COMP-2013: determinación de las resistencias y efectos secundarios a fármacos mediante el análisis de los genes implicados en la absorción, trasporte, metabolismo y excreción de fármacos

E.3

Principal inclusion criteria

1. ? 60 years of age
2. Histological confirmed DLBCL/follicular lymphoma grade IIIb by WHO classification, with any IPI (International Prognostic Index)
3. Newly diagnosed, with no previous treatment
4. Non-localised stage, i.e. lymphoma that does not fit into a single radiotherapy field (including clinical stage IA with large tumour mass until stage IV) with at least one measurable lesion
5. ECOG performance status 0 to 2
6. Present appropriate haematologic, liver (ALT or AST < 2.5 ULN ? upper limit of normal) and renal functions (creatinine < 2.5 ULN) , unless changes are secondary to lymphoma
7. LVEF at rest ? 55%, with no documented history of congestive heart failure (CHF), serious arrhythmia or acute myocardial infarction

? Pacientes con edad mayor o igual a 60 años.
? LDCBG o linfoma folicular de grado IIIB confirmado histológicamente según la clasificación Organización Mundial de la Salud (2008), con cualquier IPI.
? Pacientes de nuevo diagnóstico, sin tratamiento previo.
? Estadio no localizado, es decir linfoma que no entra en un único campo de radioterapia (incluyendo estadio clínico IA con gran masa tumoral hasta estadio IV), con al menos una lesión medible y evidencia de lesiones positivas por PET, coincidentes con las áreas anatómicas afectadas por TC.
? Estado funcional ECOG de 0 a 2.
? Pacientes con una adecuada función hematológica (neutrófilos > 1,5 x 109/l y plaquetas > 75 x 109/l; se aceptarán valores inferiores si son debidos a infiltración en médula ósea por el linfoma), hepática [ALT y AST < 2,5 x límite superior normal (LSN)] y renal (creatinina < 2,5 x LSN), salvo que las alteraciones sean secundarias al linfoma.
? FEVI en reposo ? 55%, sin antecedentes documentados de ICC, arritmias graves o infarto agudo de miocardio.

E.4

Principal exclusion criteria

1. Clinical stage I without large tumour mass or clinical stage IIA with fewer than three affected areas (stage-IIB patients are considered suitable, regardless of the number of affected areas)
2. CNS infiltration
3. Transformed lymphoma, although with no previous treatment, as well as other histological subtypes such as mantle cell lymphoma, peripheral T-cell lymphoma and its variants and post-transplant lymphoproliferative syndrome
4. Clinically significant secondary cardiovascular disease
5. Signs of any severe, acute or chronic and active infection
6. Concurrent malignancy or history of other neoplasia except basal cell carcinoma (BCC) and cervical or breast carcinoma in situ (CIN)
7. Patients with positive results in the HBV, HIV or HCV RNA tests
8. Any previous treatment for DLBCL/follicular lymphoma grade IIIb

? Estadio clínico I sin gran masa tumoral o estadio clínico IIA con menos de tres zonas afectadas (los pacientes con estadio IIB se consideran aptos, con independencia del número de zonas afectadas).
? Afectación conocida del sistema nervioso central (SNC) por el linfoma.
? Linfoma transformado, aunque nunca se hubiera tratado previamente, así como otros subtipos histológicos diferentes a los especificados en los criterios de inclusión.
? Enfermedad cardiovascular secundaria clínicamente significativa
? Indicios de cualquier infección grave, aguda o crónica y activa
? Historia previa de otras enfermedades malignas diferentes al linfoma (exceptuando el carcinoma de células basales o y carcinoma in situ de cérvix o mama)
? Pacientes con serología positiva para el VHC, VHB o el VIH.
? Cualquier tratamiento previo para el LDCBG/linfoma folicular

E.5 End points

E.5.1

Primary end point(s)

? Subclinical cardiac toxicity determined by the percentage of patients experiencing a decrease in LEVF determined by echocardiography with final LEVF <55% 30 days after the end of the study treatment

? Toxicidad cardíaca subclínica, determinada según el porcentaje de pacientes que experimentan un descenso de FEVI en reposo medida mediante ecocardiografía, alcanzando una FEVI < 55% a los 30 días tras la finalización del tratamiento del estudio

E.5.1.1

Timepoint(s) of evaluation of this end point

30 days after the end of the study treatment

30 días después de la finalización del tratamiento del estudio

E.5.2

Secondary end point(s)

? Event free survial, progression free survival and overall survival at 2 and 5 years after the end of the study treatment.
? Overall response rates and complete responses evaluated by the International Harmonization Project for response criteria in lymphoma.
? Rate of cardiac/cardiovascular toxicity according to the CTC criteria (version 4.0) of the National Cancer Institute (NCI) during the treatment and during 5 years after the end of the study treatment.
? No cardiotoxicity according to the CTC criteria (version 4.0) of the NCI during the tratment and during 24 months after the end of the study treatment.
? Cardiotoxicity determined by elevated values of troponin and NT-proBNP and decreased values of LEVF determined during the treatment and during 12 months after the end of the study treatment

? Supervivencia libre de evento, supervivencia libre de progresión y supervivencia global a los 2 años y a los 5 años tras la finalización del tratamiento.
? Tasas de respuesta global y respuesta completa al tratamiento del estudio según los criterios de respuesta para linfomas malignos del International Harmonization Project.
? Tasa de toxicidad cardíaca/cardiovascular determinada según los criterios NCI-CTCAE (versión 4) a lo largo del tratamiento y hasta los 5 años tras la finalización del mismo.
? Toxicidad no cardíaca según los criterios NCI-CTCAE (versión 4) a lo largo del tratamiento y hasta los 24 meses tras la finalización del mismo.
? Toxicidad cardíaca determinada a lo largo del tratamiento y hasta los 12 meses tras la finalización del mismo en función de la elevación de los valores de troponina y del NT-proBNP, y la disminución de la FEVI

E.5.2.1

Timepoint(s) of evaluation of this end point

During the study treatment, at the end of the study tretament and12 months, 24 months and 5 years after the end of the studyr treatment

Durante el tratamiento del estudio, a la finalización del tratamiento del estudio y a los 12 meses, 24 meses y 5 años después de la finalización del tratamiento del estudio.

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

E.6.10

Pharmacogenetic

Yes

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

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

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

Last patient last visit (5 years after the end of the study treatment)

Última visita del último paciente (a los 5 años de la finalización del tratamiento)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

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

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Disabled, blind, illiterate

Personas discapacitados, ciegos, analfabetos

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

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

None. Standard clinical care

No. Práctica clínica habitual.

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-08-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-02-17

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