Clinical Trials Register

Summary
EudraCT Number:	2012-005138-12
Sponsor's Protocol Code Number:	BRCAP-GELTAMO12
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:	2013-01-09
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

2012-005138-12

A.3

Full title of the trial

Randomized phase II study of treatment with R-CHOP vs Bortezomib-R-CAP for young patients with poor IPI diffuse large B-cell lymphoma.

Estudio fase II aleatorizado de tratamiento de los pacientes jóvenes diagnosticados de linfoma B difuso de célula grande con IPI de alto riesgo con R-CHOP vs Bortezomib-R-CAP

A.3.1

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

Randomized phase II study of treatment with R-CHOP vs Bortezomib-R-CAP for young patients with poor IPI diffuse large B-cell lymphoma.

Estudio fase II aleatorizado de tratamiento de los pacientes jóvenes diagnosticados de linfoma B difuso de célula grande con IPI de alto riesgo con R-CHOP vs Bortezomib-R-CAP

A.4.1

Sponsor's protocol code number

BRCAP-GELTAMO12

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	GELTAMO (Grupo Cooperativo Español de Linfoma/Trasplante Autólogo de Médula Ósea)
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	GELTAMO (Grupo Cooperativo Español de Linfoma/Trasplante Autólogo de Médula Ósea)
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	JANSSEN-CILAG S.A.
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	Secretaría Científica GELTAMO
B.5.2	Functional name of contact point	Ángel Cedillo
B.5.3	Address:
B.5.3.1	Street Address	c/ Fortuny Nº 51 Local 5
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28010
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034913195780NA
B.5.5	Fax number	0034913913383NA
B.5.6	E-mail	sc.geltamo@aehh.org

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	VELCADE
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	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BORTEZOMIB
D.3.2	Product code	PR-1
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	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.3.9.3	Other descriptive name	PR1
D.3.9.4	EV Substance Code	SUB20020
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	RITUXIMAB
D.3.2	Product code	PR-2
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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.3	Other descriptive name	PR-2
D.3.9.4	EV Substance Code	SUB12570MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	375
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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CICLOFOSFAMIDA
D.3.2	Product code	PR-3
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	50-18-0
D.3.9.3	Other descriptive name	PR-3
D.3.9.4	EV Substance Code	SUB06859MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	750
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ADRIAMICINA
D.3.2	Product code	PR-4
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	ADRIAMICINA
D.3.9.3	Other descriptive name	DOXORUBICIN HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB01827MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
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: 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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PREDNISONA
D.3.2	Product code	PR-5
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	PREDNISONA
D.3.9.3	Other descriptive name	PREDNISONE
D.3.9.4	EV Substance Code	SUB10020MIG
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	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	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	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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	RITUXIMAB
D.3.2	Product code	PR-6
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	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/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	375
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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CICLOFOSFAMIDA
D.3.2	Product code	PR-7
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	50-18-0
D.3.9.4	EV Substance Code	SUB06859MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	750
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 8
D.1.2 and D.1.3	IMP Role	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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ADRIAMICINA
D.3.2	Product code	PR-8
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	ADRIAMICINA
D.3.9.3	Other descriptive name	DOXORUBICIN HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB01827MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
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: 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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PREDNISONA
D.3.2	Product code	PR-9
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	PREDNISONA
D.3.9.3	Other descriptive name	PREDNISONE
D.3.9.4	EV Substance Code	SUB10020MIG
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	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	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.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	VINCRISTINA
D.3.2	Product code	PR-10
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	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/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.4
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	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

Diffuse large B cell lymphoma (DLBCL)

Linfoma B difuso de célula grande (LBDCG)

E.1.1.1

Medical condition in easily understood language

Diffuse large B cell lymphoma (DLBCL)

Linfoma difuso de célula grande B

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	14.1
E.1.2	Level	HLGT
E.1.2	Classification code	10025320
E.1.2	Term	Lymphomas non-Hodgkin's B-cell
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the proportion of patients with event-free survival at 2 years in patients diagnosed of DLBCL with aIPI > 1 or aIPI=1 with elevated levels of beta 2-mcroglobulin (above UNL).
UNL= Upper Normal Limit.

Evaluar la proporción de pacientes con supervivencia libre de evento a los 2 años, diagnosticados de LBDCG con un aIPI > 1 o aIPI = 1 con niveles elevados de beta 2-microglobulina (por encima del LSN).
LSN= Límite superior de normalidad.

E.2.2

Secondary objectives of the trial

1. Event -free survival at 2 years in differents biological DLBCL subgroups: CGB vs non-CGB.
2. Overall survival at 2 years in patients diagnosed of DLBCL with aIPI > 1 or aIPI=1 with elevated levels of beta 2-microglobulin (above UNL).
3. Overall response rate and complete remissions in patients diagnosed of DLBCL with aIPI > 1 or aIPI=1 with elevated levels of beta 2-mcroglobulin (above UNL).
4. Toxicity according to the CTC criteria (version 3.0) of the National Cancer Institute (NCI). http://ctep.cancer.gov/reporting/ctcnew.html)
5. To evaluate the predictive value for EFS of interim PET/CT evaluation after 2 and 4 cycles of chemotherapy.
6. To identify clinical and biological prognostic factors for response and survival.

1. Evaluar la supervivencia libre de evento a los 2 años en los diferentes subtipos biológicos de LBDCG: GCB vs no-GCB.
2. Evaluar la supervivencia global a los 2 años en pacientes diagnosticados de LBDCG con un aIPI > 1 o aIPI = 1 con niveles elevados de beta 2-microglobulina (por encima del LSN).
3. Evaluar la respuesta global y la tasa de remisiones completas en pacientes diagnosticados de LBDCG con un aIPI > 1 o aIPI = 1 con niveles elevados de beta 2-microglobulina.
4. Evaluar la toxicidad del tratamiento según los criterios CTC (versión 3.0) del National Cancer Institute (NCI). (http://ctep.cancer.gov/reporting/ctcnew.html).
5. Evaluar el valor predictivo para la SLE del PET/TC tras 2 y 4 ciclos de quimioterapia.
6. Identificar factores predictores de respuesta y supervivencia tanto clínicos como biológicos (ver anexo del proyecto biológico).

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

Biology Project: V2.0 - 15th February, 2013
- To explore the mutational profile in a selection of these cases by massive sequencing.
- To analyze the impact of the molecular classification of DLBCL based on IHC (as Hans algorithms, Choi and Meyer) in the prospective series of the patients of this clinical trial.
- To explore the effect of the expression of genes, miRNAs and proteins of interest. Refine the IHC analysis with automatic quantification methods of protein expression.
- To explore the effect of frequent cytogenetic alterations in DLBCL.

PET SCAN PROJECT: V2.0 - 15th, February 15 2013
Qualitative and quantitative, prospective central review of the PET scans performed before treatment, after second cycle, after fourth cycle and after treatment completion.
The PET Network group of GELTAMO, compound of five experts in PET scans, will conduct this blind central review in real-time.

PROYECTO BIOLOGICO: versión 2.0 del 15 de Febrero de 2013
- Explorar el perfil mutacional en una selección de estos casos mediante secuenciación masiva.
- Analizar el impacto de la clasificación molecular del LBDCG basada en IHQ (según los algoritmos de Hans, Choi y Meyer) en la serie prospectiva de pacientes del ensayo clínico.
- Explorar el efecto de la expresión de genes, miRNAs y proteínas de interés. Refinar el análisis IHQ con métodos de cuantificación automática de la expresión proteica.
- Explorar el efecto de alteraciones citogenéticas frecuentes en LBDCG.

PROYECTO DE TOMOGRAFÍA POR EMISIÓN DE POSITRONES (PET): versión 2.0 del 15 de Febrero de 2013
valoración centralizada prospectiva cualitativa y cuantitativa de los estudios PET realizados antes del comienzo del tratamiento así como después del segundo ciclo (sin que el resultado de la PET cambie el tratamiento) y tras 4 ciclos (pudiendo cambiar el resultado de la PET la línea de QT). También se realizará y analizará una PET final tras completar el tratamiento para valorar el estado de remisión.
El grupo PET Network de GELTAMO, compuesto por cinco médicos nucleares expertos en PET/CT, realizará una revisión centralizada ciega en tiempo real de los estudios PET.

E.3

Principal inclusion criteria

1.- Patients diagnosed with primary diffuse DLBCL who have never received treatment for this condition.
2.- Age between 18 and 70 years.
3.- Age adjusted IPI higher than 1 or equal 1, with high levels of beta-2-microglobulin (above UNL)
4.- Neoplasic B lymphocytes for CD20 positivity.
5.- ECOG 0-3
6.- More than 12 weeks of life expectancy.
7.- Signed Informed Consent.
8.- Nor pregnant women nor breast-feeding women without heterosexual activity during the entire study. Women with heterosexual activity only if they are willing to use two methods of contraceptive. The two contraceptive methods can be, two barrier method or a barrier method combinated with an hormonal contraceptive method to prevent pregnancy, used during the entire study and until 3 months after the study completion.

1. Pacientes diagnosticados de LDCGB primario no localizado que nunca hayan recibido quimioterapia previa.
2. Pacientes entre 18 y 70 años.
3. IPI ajustado por edad aIPI>1 o aIPI=1 con niveles elevados de beta 2-microglobulina (por encima del LSN).
4. Positividad de los linfocitos B neoplásicos para el CD20.
5. Puntuación en la escala funcional ECOG de 0 a 3.
6. Esperanza de vida mayor a 12 semanas.
7. Consentimiento informado por escrito
8. Mujeres no embarazadas ni lactantes sin actividad heterosexual durante la totalidad del estudio. Mujeres con actividad heterosexual solamente si están dispuestas a utilizar 2 métodos anticonceptivos. Los 2 métodos anticonceptivos pueden ser 2 métodos de barrera o un método de barrera y un método hormonal para prevenir el embarazo, utilizados durante la totalidad del estudio y hasta 3 meses tras la finalización del mismo.

E.4

Principal exclusion criteria

1. Pregnant women or in breast-feeding period, or adults in childbearing period not using an effective contraception method.
2. Patients with CNS lymphoma
3. Patients with severe impairment of renal function (creatinine> 2.5 UNL) or hepatic (bilirubin or ALT / AST> 3 UNL), unless it is suspected to be due to the disease.
4. HIV positive patients
5. Patient previously treated for the DLBCL
6. Positive determination of chronic hepatitis B (defined as positive serology for HBsAg). It will be allowed to enroll patients with hidden or previuos hepatitis (defined as positive antibodies against the core of the hepatitis B virus [HBcAb] and HBsAg negative) if undetectable HBV DNA.
7. Positive results for hepatitis C (antibody serology for hepatitis C virus [HCV]). Patients with HCV positive may participate only if the result of the PCR is negative for HCV RNA.
8.Patients with previous history of cardiac disease: ventricular ejection fraction < 50%.
9. Patients with severe psiquiatric conditions that may interfere with their ability to understand the study (including alcoholism or drug addiction).
10. Patients with known hypersensitivity to murine proteins or any other component of the study drugs.
11. Transformed follicular lymphoma.
12. History of other primary malignancy with < 5 year of complete response (except for basal or squamous cell carcinomas of the skin or cervical carcinoma in situ).
13. Uncontrolled current illness: cardiac, pulmonary, neurologic, metabolic etc, not related to lymphoma.
14. Uncontrolled hypertension (diastolic blood pressure over 110 mmHg).
15. Psychiatric illnesses that could compromise the patient participation in the study.
16. Known or suspected hypersensitivity to any of the agents of the study.

1. Mujeres embarazadas o en periodo de lactancia, o adultos en edad fértil que no utilicen un método contraceptivo eficaz.
2. Pacientes con linfoma del SNC.
3. Pacientes con deterioro severo de la función renal (creatinina > 2,5 UNL) o hepática (bilirrubina o ALT/AST > 3 UNL), excepto si se sospecha que se debe a la propia enfermedad.
4. Pacientes positivos para el HIV
5. Pacientes previamente tratados de LDCGB.
6. Resultados positivos de las pruebas de hepatitis B crónica (definida por la serología positiva para HBsAg). Se podrán reclutar pacientes con hepatitis B oculta o previa (que se define por anticuerpos contra el núcleo del virus de la hepatitis B [HBcAb] positivos y HBsAg negativo) si el ADN del VHB es indetectable.
7. Resultados positivos para la hepatitis C (serología de anticuerpos contra el virus de la hepatitis C [VHC]). Los pacientes VHC positivos solo podrán participar si el resultado de la PCR es negativo para el ARN del VHC.
8. Pacientes con historia previa de cardiopatía con fracción de eyección <50%.
9. Pacientes con enfermedades psiquiátricas graves que puedan interferir con su habilidad para entender el estudio (incluyendo alcoholismo o drogadicción).
10. Pacientes con hipersensibilidad conocida a las proteínas murinas o a cualquier otro componente de los medicamentos del estudio.
11. Linfoma folicular transformado.
12. Historia de otra neoplasia maligna con < 5 años de remisión completa (excepto el carcinoma escamoso cutáneo y el carcinoma de cérvix in situ).
13. Enfermedades de base no controladas: cardiacas, respiratorias, neurológicas, metabólicas, etc., no relacionadas con el linfoma.
14. Hipertensión arterial no controlada (tensión arterial diastólica de más de 110 mmHg).
15. Enfermedades psiquiátricas que puedan comprometer la participación del paciente en el estudio.
16. Hipersensibilidad conocida o sospechada a cualquiera de los agentes del régimen en evaluación.

E.5 End points

E.5.1

Primary end point(s)

Propotion of patients with event -free survival at 2 years.

La variable principal de valoración es la proporción de pacientes con supervivencia libre de evento (SLE) a los 2 años.

E.5.1.1

Timepoint(s) of evaluation of this end point

Once the treatment is started, there will be weekly safety visits, visits before each treatment cycle, at day 60 after the sixth cycle and then follow-up visits every three months during the first 2 years and every 6 months until the 5th year.

Una vez se inicie el tratamiento del ensayo, se realizarán visitas previas al inicio de cada ciclo, semanalmente visitas de seguridad, a los 60 días de finalizar los 6 ciclos de tratamiento y visitas de seguimiento cada 3 meses los 2 primeros años y cada 6 meses hasta el 5º año.

E.5.2

Secondary end point(s)

- Event -free survival at 2 years.
- Overal survival at 2 years.
- Complete remission rate.
- Complete remision rate not documented/not confirmed.
- Partial remission rate.
- Stable Disease rate, progression.
- Relapsed Disease rate.
- Proportion of subjects who have received all planned chemotherapy dose on schedule.
- Proportion of cycles of chemotherapy administered in planned doses and on schedule.
- Clinical predictors factors of response.
- Safety endpoints from cycle 1 to 6.
- Prognostic value of PET in terms of survival.
- Biological prognostic factors, including histologic subtype CGB vs non-CGB.

Supervivencia libre de evento a los 2 años.
Supervivencia global (SG) a los 2 años.
Tasa de remisión completa (RC).
Tasa de remisión completa no documentada / no confirmada (RCu).
Tasa de respuesta parcial (RP).
Tasa de enfermedad estable (EE), progresión (P).
Tasa de recaída(R).
Proporción de sujetos que reciben todas las dosis de quimioterapia planificadas en el tiempo previsto.
Proporción de ciclos de quimioterapia administrados en las dosis planificadas y en el tiempo previsto.
Factores clínicos predictores de respuesta: sexo, edad, estadío, ECOG, LDH, ?2-microglobulina, enfermedad voluminosa, número de localizaciones nodales, número de localizaciones extranodales.
Variables de seguridad en los ciclos 1 a 6.
Valor pronóstico del PET/TC tras los ciclos 2 y 4 en la supervivencia.
Factores pronósticos biológicos, incluido el subtipo histológico CGB vs no-CGB.

E.5.2.1

Timepoint(s) of evaluation of this end point

Once the treatment is started, there will be weekly safety visits, a visit before each treatment cycle, a visit at day 60 after the sixth cycle and then follow-up visits every three months the first 2 years and every 6 months until the 5th year.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

The Trial will be considered closed when the data of the primary and secondary endpoints will be sufficiently prepared for their initial publication.

El ensayo se considerará cerrado desde el punto de vista normativo después de que los datos sobre las variables primarias y secundarias estén lo suficientemente preparados para su publicación inicial.

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:

127

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

127

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

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

127

F.5

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

Expected normal treatment of that condition.

Tratamiento habitual previsto para esta patología.

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

2013-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-07

P. End of Trial
P.	End of Trial Status	Completed

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