Clinical Trials Register

Summary
EudraCT Number:	2008-007305-36
Sponsor's Protocol Code Number:	GEL-TAMO/R-GemOx-08-04/v2
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:	2009-03-09
Trial results

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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2008-007305-36

A.3

Full title of the trial

Estudio fase II prospectivo, abierto, multicéntrico de Gemcitabina, Oxaliplatino y Dexametasona + Rituximab en pacientes con linfomas agresivos (difuso de céluls grandes B y del manto) en recaída o resistencia no subsidiarios de ser sometidos a quimioterapia intensa y trasplante autólogo de progenitores hemocitopoyéticos.

A.3.2

Name or abbreviated title of the trial where available

GEL-TAMO/R

A.4.1

Sponsor's protocol code number

GEL-TAMO/R-GemOx-08-04/v2

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GELTAMO (Grupo Español de Linfoma y Transplante 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	GEMZAR 1000 mg polvo para solución para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	LILLY, S.A.
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
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	GEMCITABINA HIDROCLORURO
D.3.9.3	Other descriptive name	GEMCITABINE HYDROCHLORIDE
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	1000
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	Information not present in EudraCT
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	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 for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	RITUXIMAB
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	ELOXATIN 5 mg/ml concentrado para solución para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI AVENTIS, S.A.
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
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	OXALIPLATINO
D.3.9.3	Other descriptive name	OXALIPLATINO
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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

Linfoma difuso de células grandes B y Linfoma del manto

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9
E.1.2	Level	LLT
E.1.2	Classification code	10012821
E.1.2	Term	Diffuse large B-cell lymphoma recurrent

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9
E.1.2	Level	LLT
E.1.2	Classification code	10026800
E.1.2	Term	Mantle cell lymphoma recurrent

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluar la eficacia y tolerancia del esquema rituximab, gemcitabina, oxaliplatino dexametasona (R-GemOx) en términos de respuesta completa global y respuesta completa, así como su tolerancia y toxicidad

E.2.2

Secondary objectives of the trial

1. Evaluar la toxicidad del régimen R-GemOX.
2. Evaluar si el balance eficacia/toxicidad permite la posibilidad de posteriores intervenciones con el fin de prolongar la supervivencia libre de progresión (SLP) y la supervivencia global (SG), tales como tratamientos de consolidación y/o mantenimiento. Por tanto, el estado general (ECOG) no será un criterio de exclusión, a menos que el paciente sea incapaz de comprender la finalidad del ensayo y sus riesgos.
3. Identificar los factores clínicos predictores de respuesta.
4. Evaluar el cumplimiento terapéutico de los ciclos de tratamiento con R-GemOx por lo que respecta a retrasos en la administración de los ciclos y a reducciones de la dosis quimioterápica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Edad igual o superior a 18 años.
2. Pacientes diagnosticados de LDCGB y LM en resistencia primaria o en recaída que no sean susceptibles de ser sometidos a intensificación quimioterápica seguida de TAPH por edad, comorbilidad o TAPH previo.
3. Cualquier IPI o ECOG, siempre que sean capaces de entender la naturaleza del ensayo.
4. Consentimiento informado por escrito

E.4

Principal exclusion criteria

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 > 2,5 UNL), excepto si se sospecha que se debe a la propia enfermedad.
4. Pacientes positivos para el HIV.
5. Pacientes con enfermedades psiquiátricas graves que puedan interferir con su habilidad para entender el estudio (incluyendo alcoholismo o drogadicción).
6. Pacientes con hipersensibilidad conocida a las proteínas murinas o a cualquier otro componente de los medicamentos del estudio.
7. Pacientes que hayan recibido más de 2 líneas terapéuticas previas. (en el caso de haber sido sometidos a TAPH previamente, el tratamiento de inducción junto con el de acondicionamiento para el TAPH se considerará una sola línea terapéutica)

E.5 End points

E.5.1

Primary end point(s)

Se aplicarán los criterios del International Workshop to Standarize Response Criteria for NHL (Seminario internacional para la normalización de los criterios de respuesta del LNH (Criteria for evaluation of response in Non-Hodgkin's Lymphoma, criterios para la evaluación de la respuesta en el linfoma no-Hodgkin, Cheson, 1999)

a) RESPUESTA COMPLETA (RC)

1. Desaparición completa de la masa tumoral detectada mediante las técnicas radiológicas diagnósticas aplicadas, con desaparición de síntomas constitucionales o relacionados con afectación directa por el tumor, y normalización de los parámetros bioquímicos anormales (LDH)

2. Reducción de todos los ganglios linfáticos y masas ganglionares a un tamaño menor o igual a 1,5 cm en su diámetro transverso mayor, en aquellos casos con adenopatías >1,5cm al diagnóstico, o menor o igual a 1 cm en aquellos casos con tamaño de 1,1 a 1,5 cm al diagnóstico.

3. Desaparición de esplenomegalia clínica y radiológica, así como otros órganos aumentados al diagnóstico.

4. Aspirado-Biopsia de médula ósea normal sobre la base de criterios morfológicos (celularidad normal en aspirado con <30% linfocitos y ausencia de infiltración linfocitaria en médula ósea9, la muestra de biopsia debe ser adecuada (>2cm)

b) RESPUESTA COMPLETA NO CONFIRMADA (RCnC)

Se incluyen aqullos casos que reúnen los criterios 1 y 3, pero que además presentan algunos de los rasgos siguientes:

1. Linfadenopatía aislada o conglomerado adenopático mayor o igual a 1,5 cm en su diámetro transverso mayorque ha reducido su tamaño original en más de un 75%.

2. Incremento del número o tamaño de nódulos linfoides en médula ósea sin alteraciones morfológicas o estructurales evidentes (médula ósea indeterminada).

c) RESPUESTA PARCIAL (RP)

1. reducción mayor o igual al 50% de las masas correspondientes a las 6 áreas linfoides mayores.

2. No aumentos de áreas ganglionares ausentes al diagnóstico o aparición de nuevas masas tumorales.

3. Reducción mayor o igual al 50% de nódulos o masas hepáticas o esplénicas.

4. La afectación de otros órganos se considera evaluable pero no medible a menos que se realice biopsia de los mismos; la valoración de la médula ósea se considera irrelevante para la determinación de RP porque se considera evaluable pero no medible.

d) ENFERMEDAD ESTABLE (EE)

Se define como obtención de respuesta menor a la respuesta parcial, pero sin progresión de la enfermedad.

e) ENFERMEDAD PROGRESIVA (en RP o EE)

Incremento >50% ebn la suma de los productos de los diámetros mayores de las adenopatías afectas en casos etiquetados de RP o aparición de nuevas lesiones durante o al final del tratamiento.

f) RECIDIVA (en RC o RCnC)

1. Aparición de nuevas lesiones o incremento mayor o igual al 50% de las lesiones anteriores.

2. Incremento mayor o igual al 50% del diámetro mayor de cualquiera de las masas anteriores quemidiesen mayor o igual a 1cm.

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

Information not present in EudraCT

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

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

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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.8.5

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

Information not present in EudraCT

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

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	No
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.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	129

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

2009-05-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-01-09

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

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