Clinical Trials Register

Summary
EudraCT Number:	2006-003563-31
Sponsor's Protocol Code Number:	26866138CAN 2021
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2008-03-07
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

2006-003563-31

A.3

Full title of the trial

Estudio de fase II con Bortezomib, Dexametasona y Rituximab en combinación, en pacientes con Macroglobulinemia de Waldenström (MW) sin tratamiento previo (Phase II Study of Combination Bortezomib, Dexamethasone, and Rituximab in previously untreated Patients with Waldenstrom’s Macroglobulinemia)

A.3.2

Name or abbreviated title of the trial where available

protocol BDR

A.4.1

Sponsor's protocol code number

26866138CAN 2021

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	Red Europea de Mieloma (European Myeloma Network)
B.1.3.4	Country	Netherlands
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	Velcade
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Cilag International N.V.
D.2.1.2	Country which granted the Marketing Authorisation	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.3.1	Product name	Velcade
D.3.4	Pharmaceutical form	Powder for solution for injection
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.3.9.3	Other descriptive name	BORTEZOMIB
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	3.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	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.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
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration 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.3.1	Product name	Mabthera
D.3.2	Product code	RO045-2294
D.3.4	Pharmaceutical form	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	1747222-31
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	500
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)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
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	Fortecortin 40
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK FARMA Y QUIMICA, S.A.
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.3.1	Product name	Fortecortin
D.3.4	Pharmaceutical form	Powder for injection*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 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.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	Fortecortin 40
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK FARMA Y QUIMICA, S.A.
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.3.1	Product name	Fortecortin
D.3.4	Pharmaceutical form	Powder for injection*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 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

Macroglobulinemia de Waldenström (MW) [Waldenstrom’s Macroglobulinemia]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10054695
E.1.2	Term	Waldenstrom's macroglobulinemia

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Determinar la tasa de respuestas [combinando respuesta completa (RC) + respuesta parcial (RP) + respuesta mínima (RM)] tras el tratamiento con Bortezomib, Dexametasona y Rituximab (BDR) en paciente con Macroglobulinemia de Waldenström sin tratamiento previo.

E.2.2

Secondary objectives of the trial

• Determinar el tiempo hasta la progresión tras tratamiento con BDR
• Determinar la eficacia y tolerancia de Bortezomib, Dexametasona y Rituximab en pacientes con Macroglobulinemia de Waldenström.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Diagnóstico clínico-patológico de macroglobulinemia de Waldenstrom, tal como define el grupo consenso uno del Segundo Taller Internacional sobre macroglobulinemia de Waldenstrom. Todos los pacientes con el diagnóstico de MW se evaluarán para determinar su respuesta según el criterio de respuesta (sección 9.1).
• Sin tratamiento sistémico anterior para la MW. Está permitido que el paciente haya sido sometido a plasmaféresis con anterioridad para controlar la hiperviscosidad. En este caso, los niveles de proteí-na monoclonal inicial para la evaluación de la respuesta serán los niveles anteriores a la plasmaféresis, si éste es el valor más alto antes del inicio del tratamiento.
• Los pacientes deben tener al menos una de las siguientes indicaciones para iniciar el tratamiento, tal como se define por las recomendaciones del “Grupo Consenso Dos” Del Segundo Taller Internacio-nal sobre Macroglobulinemia de Waldenstrom.
- Fiebre recurrente, sudores nocturnos, pérdida de peso, fatiga.
- Hiperviscosidad.
- Linfadenopatía que es o bien sintomática o bien voluminosa (≥ 5 cm de diámetro máximo).
- Hepatomegalia y/o esplenomegalia sintomática.
- Organomegalia sintomática y/o infiltración de tejidos y órganos
- Neuropatía periférica debida a MW.
- Crioglobulinemia sintomática.
- Anemia por crioaglutinina.
- Trombocitopenia y/o anemia hemolítica inmunitaria.
- Nefropatía relacionada con MW.
- Amiloidosis relacionada con MW.
- Hemoglobina ≤ 10 g/dL.
- Recuento de plaquetas < 100 · 10e9/L.
- Proteína monoclonal sérica > 5 g/dL incluso sin síntomas.

• Enfermedad positiva para CD20 basándose en cualquier análisis de citometría de flujo o inmunohistoquímica anterior de la médula ósea realizado hasta 3 meses antes de la inclusión.
• Estado general de Karnofsky > 60.
• Esperanza de vida >3 meses.
• Recuento de plaquetas en el nivel inicial > 50 · 10e9/L, y recuento absoluto de neutrófilos > 0,75 · 10e9/L.
• Cumplir los siguientes criterios de laboratorio antes del tratamiento en la visita de selección realizada en el plazo de 28 días de la inclusión del estudio:
- AST (SGOT): < 3 veces el límite superior al normal del laboratorio institucional.
- ALT (SGPT): < 3 veces el límite superior al normal del laboratorio institucional.
- Bilirrubina total: < 2 veces el límite superior al normal del laboratorio institucional, a menos que esté claramente relacionado con la enfermedad.
- Aclaramiento de creatinina medido o calculado: > 30 mL/minuto.
- Sodio sérico >130 mmol/L.

• Consentimiento informado por escrito voluntario antes de la realización de cualquier procedimiento relacionado con el estudio que no forme parte de la atención médica normal, entendiendo que el su-jeto puede retirar el consentimiento en cualquier momento sin perjuicio de su atención médica en el futuro.

E.4

Principal exclusion criteria

• Tratamiento sistémico anterior con MW (se permite la plasmaféresis).
• Infarto de miocardio en el plazo de 6 meses antes de la inclusión o tiene Clase III o IV según la New York Hospital Association (NYHA) (Asociación Cardiológica de Nueva York) o insuficiencia cardiaca, angina no controlada, arritmias ventriculares no controladas graves, o evidencia electrocardiográfica de isquemia aguda o anomalías en el sistema de conducción activo. Antes de la entrada en el estu-dio, el investigador tiene que documentar cualquier anomalía ECG en la selección como no médica-mente relevante.
• El paciente tiene hipersensibilidad a dexametasona, bortezomib, boro o manitol.
• Enfermedad psiquiátrica o médica grave que probablemente interfiera con la participación en este estudio clínico.
• Amiloidosis cardiaca.
• Neuropatía periférica o dolor neuropático de grado 2 o superior, tal como se define por la versión 3 de CTCAE (Common Terminology Criteria for Adverse Events, Criterios de terminología comunes para acontecimientos adversos) del NCI
• Mujeres que estén embarazadas. Mujeres que estén en el periodo de lactancia y no consientan en suspender la lactancia. Mujeres en edad de procrear que no estén dispuestas a utilizar métodos anticonceptivos eficaces durante la duración del estudio y 6 meses después. Hombres que no consien-tan en no tener un niño durante el periodo de tratamiento y seis meses después.

E.5 End points

E.5.1

Primary end point(s)

• Determinar la tasa combinada de respuestas [respuesta completa (RC) + respuesta parcial (RP) + respuesta mínima (RM)] tras tratamiento con BDR en pacientes con Macroglobuinemia de Waldenström sin tratamiento previo.

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

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

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

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

End of trial in a Member State
End of trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient patients have been recruited and completed the trial as stated in the regulatory application, in the Member State. Poor recruitment (recruiting less than anticipated number) by a Member State is not a reason for premature termination.

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

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-03-07.

Yes

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

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)

Not applicable

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

2008-04-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-22

P. End of Trial
P.	End of Trial Status	Ongoing

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