Clinical Trials Register

Summary
EudraCT Number:	2010-024215-14
Sponsor's Protocol Code Number:	C25001
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:	2012-04-26
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

2010-024215-14

A.3

Full title of the trial

A Randomized, Open-Label, Phase 3 Trial of brentuximab vedotin (SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma

Estudio en fase 3, abierto, aleatorizado con brentuximab vedotin (SGN-35) frente al tratamiento de elección del investigador (metotrexato o bexaroteno) en pacientes con linfoma cutáneo de células T CD30 positivo

A.3.1

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

Study of Bretuximab Vedotin Compared to Physician's Choice in Patients With CD30-Positive Cutaneous T-Cell Lymphoma

Estudio de Bretuximab Vedotin comparado con tratamiento elegido por el investigador en pacientes con linfoma cutáneo de células T CD30 positivo

A.4.1

Sponsor's protocol code number

C25001

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	Millennium Pharmaceuticals, Inc
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Millennium Pharmaceuticals, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Millennium, Drug Information Call Centre
B.5.2	Functional name of contact point	Drug Information Call Centre
B.5.3	Address:
B.5.3.1	Street Address	40 Landsdowne Street
B.5.3.2	Town/ city	Cambridge, Massachssetts
B.5.3.3	Post code	MA 02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+115107402412
B.5.5	Fax number	+118008816092
B.5.6	E-mail	medical@mlnm.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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/11/939
D.3 Description of the IMP
D.3.1	Product name	Brentuximab vedotin
D.3.2	Product code	SGN-35
D.3.4	Pharmaceutical form	Powder 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	Brentuximab vedotin
D.3.9.1	CAS number	914088-09-8
D.3.9.2	Current sponsor code	SGN-35
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	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	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 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	Methotrexate
D.2.1.1.2	Name of the Marketing Authorisation holder	Goldshield Pharmaceuticals Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	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	METHOTREXATE
D.3.9.1	CAS number	59-05-2
D.3.9.4	EV Substance Code	SUB08856MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	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	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	Targretin
D.2.1.1.2	Name of the Marketing Authorisation holder	Eisai Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, soft
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	BEXAROTENE
D.3.9.1	CAS number	153559-49-0
D.3.9.4	EV Substance Code	SUB00795MIG
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	75
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

CD30-Positive Cutaneous T-Cell Lymphoma

linfoma cutáneo de células T CD30 positivo

E.1.1.1

Medical condition in easily understood language

A type of cancer of the immune system requiring treatment.

Tipo de cáncer del sistema inmunológico que requiere tratamiento.

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	LLT
E.1.2	Classification code	10011677
E.1.2	Term	Cutaneous T-cell lymphoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 determine ORR, lasting at least 4 months, with brentuximab
vedotin in patients with CD30+ MF or pcALCL compared to that achieved with therapy in the control arm

Determinar la tasa de respuesta global (TRG), de 4 meses de duración como mínimo, asociada a brentuximab vedotin en pacientes con MF o LACGcp CD30+, en comparación con la lograda con el tratamiento en el grupo de control.

E.2.2

Secondary objectives of the trial

CR rate with brentuximab vedotin compared to that achieved with
therapy in the control arm

Determinar la tasa de respuesta completa (RC) con brentuximab vedotin en comparación con la lograda con el tratamiento en el grupo de control.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Voluntary consent form
- Male or female patients 18 years or older with diagnosis of MF or pcALCL
- Histologically confirmed CD30+ disease by central laboratory
assessment and pathology review
- Eastern Cooperative Oncology Group (ECOG) performance status ?2
- Female patients who are post menopausal, surgically sterile,
or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
- Male patients who agree to practice effective barrier
contraception or agree to abstain from heterosexual intercourse
- Clinical laboratory value as specified in protocol

- Consentimiento Voluntario
- Pacientes de uno u otro sexo con una edad mínima de 18 años y diagnóstico de MF o de LACGcp.
- Enfermedad CD30+ confirmada histológicamente por la evaluación del laboratorio central y la revisión anatomopatológica.
- Estado funcional del Eastern Cooperative Oncology Group (ECOG) ? 2 (véase el apartado 15.1).
- Mujeres que son posmenopáusicas durante al menos un año antes de la visita de selección o son estériles por motivos quirúrgicos, o si están en edad fértil, se comprometen a emplear dos métodos anticonceptivos eficaces al mismo tiempo, desde el momento en que se firme el consentimiento informado y hasta 30 días después de la última dosis del medicamento del estudio o se comprometen a abstenerse completamente de mantener relaciones heterosexuales.
- Varones, aun cuando estén esterilizados quirúrgicamente que se comprometen a emplear un método anticonceptivo de barrera eficaz durante todo el período de tratamiento del estudio y hasta 6 meses después de la última dosis del medicamento del estudio, o se comprometen a abstenerse completamente de mantener relaciones heterosexuales.
- Valores analíticos que se especifican en el protocolo

E.4

Principal exclusion criteria

- A concurrent diagnosis of systemic ALCL, other non Hodgkin
lymphoma(excluding LyP) or Sezary syndrome
- Patients with cardiovascular conditions specified in protocols
- Patients with history of another primary malignancy not in
remission for at least 3 years
- Known active cerebral/meningeal disease, HIV infection, hepatitis B or Hepatitis C infection
- Oral retinoid therapy for any indication within 12 weeks of
study entry
- Corticosteroid therapy within 4 weeks or immunosuppressive
chemotherapy or any immunotherapy within 12 weeks of
first dose of study drug
- Female patients who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on

- Diagnóstico simultáneo de LACG sistémico u otro linfoma no hodgkiniano (a excepción de LACGcp) o síndrome de Sézary.
- Cualquiera de las enfermedades cardiovasculares especificadas en el protocolo
- Antecedentes de otra neoplasia maligna primaria que no ha estado en remisión durante al menos 3 años.
- Enfermedad cerebral/meníngea activa conocida, incluidos signos o síntomas de leucoencefalopatía multifocal progresiva (LMP).
- Infección por el VIH conocida.
- Hepatitis B con antígeno de superficie positivo conocida, o bien hepatitis C activa conocida o sospechada.
- Cualquier infección sistémica viral, bacteriana o micótica activa que requiera tratamiento antimicrobiano sistémico en las 2 semanas anteriores a la primera dosis de medicamento del estudio.
- Recepción de quimioterapia inmunodepresora o de cualquier tipo de inmunoterapia (por ejemplo, reposición de inmunoglobulinas u otros tratamientos con anticuerpos monoclonales) en las 12 semanas anteriores a la primera dosis de medicamento del estudio.
- Tratamiento con corticoides en las 4 semanas anteriores a la primera dosis de medicamento del estudio.
- Hipersensibilidad conocida a proteínas recombinantes, a proteínas murinas o a alguno de los excipientes contenidos en la formulación del medicamento.
- Mujeres que estén en período de lactancia o que tengan una prueba de embarazo en suero positiva durante el período de selección o una prueba de embarazo en orina positiva el día 1 de cualquier ciclo.
- Tratamiento con radioterapia o con cualquier producto en investigación en los 21 días anteriores a la primera dosis de medicamento del estudio.
- Progresión durante el tratamiento previo con bexaroteno y metotrexato.
- Tratamiento con retinoides orales por cualquier indicación en las 12 semanas anteriores a la incorporación al estudio.
- Tratamiento sistémico con vitamina A en dosis superiores a 15.000 UI (5000 µg) al día (equivalente a aproximadamente 3 veces el aporte diario recomendado) en los 30 días anteriores a la primera dosis de medicamento del estudio.
- Antecedentes de pancreatitis o factores de riesgo importantes de pancreatitis.

E.5 End points

E.5.1

Primary end point(s)

To determine the proportion of patients achieving an objective response that lasts at least 4 months

Determinar la proporción de pacientes que logren una respesta objetiva de 4 meses de duración como mínimo según el CRI

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of cycles 3,6,9,12, and 15; at EOT; then every
12 weeks for a minimum of 24 months, and then every 6 months until disease progression or study closure

Al final de los ciclos 3, 6, 9, 12 y 15; al final del tratamiento. Posteriormente cada 12 semanas durante un mínimo de 24 meses y posteriormente cada 6 meses hasta progresión de la enfermedad o cierre del ensayo.

E.5.2

Secondary end point(s)

To determine the proportion of patients achieving complete response (CR)

Determinar la proporción de pacientes que logren Respuesta Completa (RC).

E.5.2.1

Timepoint(s) of evaluation of this end point

Does not have a specific timepoint.

No hay visita específica.

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.6.13.1

Other scope of the trial description

Immunogenicity and biomarker analysis

Inmunogenicidad y análisis de biomarcadores

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Belgium

Brazil

France

Germany

Italy

Netherlands

Poland

Spain

Switzerland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

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

Last visit of the last subject.

última visita del último paciente

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

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

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

105

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

124

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)

For patients who complete 16 cycles of brentuximab vedotin, re-initiation of brentuximab vedotin may be permitted at the joint discretion of the sponsor and investigator. For patients who complete 48 weeks of reference theraphy, initiation of subsequent standard-of-care theraphy should be discussed with the study doctor.

En los pacientes que hayan sido tratados con 16 ciclos de brentuximab vedotin, se permitirá el reinicio del tratamiento con brentuximab vedotin bajo el criterio conjunto del promotor y del investigador. Para los pacientes que hayan completado 48 semanas de tratamiento de referencia, se discutirá el inicio de la terapia estándar posterior con el investigador del estudio.

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

2012-06-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-07-06

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