Clinical Trials Register

Summary
EudraCT Number:	2007-003945-33
Sponsor's Protocol Code Number:	RV-MM-PI-280
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-07-29
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

Germany - BfArM

A.2

EudraCT number

2007-003945-33

A.3

Full title of the trial

A randomised comparison of daily 25 mg versus 5 mg lenalidomide as maintenance therapy after high-dose therapy and autologous stem cell transplantation in patients with multiple myeloma.

Randomisierter Vergleich von 25 mg versus 5 mg Lenalidomid als Erhaltungstherapie nach Hochdosistherapie und autologer Blutstammzelltransplantation bei Patienten mit Multiplen Myelom

A.3.1

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

A randomised comparison of daily 25 mg versus 5 mg lenalidomide as maintenance therapy after high-dose therapy and autologous stem cell transplantation in patients with multiple myeloma.

Randomisierter Vergleich von 25 mg versus 5 mg Lenalidomid als Erhaltungstherapie nach Hochdosistherapie und autologer Blutstammzelltransplantation bei Patienten mit Multiplen Myelom

A.3.2

Name or abbreviated title of the trial where available

LenaMain

A.4.1

Sponsor's protocol code number

RV-MM-PI-280

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	Gesellschaft für Medizinische Innovation –Hämatologie und Onkologie mbH (GMIHO)
B.1.3.4	Country	Germany
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	Fa. Celgene
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gesellschaft für Medizinische Innovation –Hämatologie und Onkologie mbH (GMIHO)
B.5.2	Functional name of contact point	CRA - Clinical Research Associate
B.5.3	Address:
B.5.3.1	Street Address	Alte Jakobstraße 77
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10179
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4935125933280
B.5.5	Fax number	+4935125933289
B.5.6	E-mail	info@gmiho.de

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	Revlimid (5 mg)
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/177
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
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	Lenalidomide
D.3.9.1	CAS number	191732-72-6
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	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: 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	Revlimid (10mg)
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/177
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
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	Lenalidomide
D.3.9.1	CAS number	191732-72-6
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Revlimid (25mg)
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/177
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
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	Lenalidomide
D.3.9.1	CAS number	191732-72-6
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	25
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

Patients with multiple myeloma

Multiples Myelom

E.1.1.1

Medical condition in easily understood language

multiple myeloma

Multiples Myelom

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	16.1
E.1.2	Level	HLT
E.1.2	Classification code	10028229
E.1.2	Term	Multiple myelomas
E.1.2	System Organ Class	100000004851

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

Compare the event-free survival (EFS) of patients with multiple myeloma who receive two different dose levels (25 vs. 5 mg daily) of lenalidomide as maintenance therapy after first line high-dose therapy and autologous stem cell transplantation.

- Wirksamkeit durch Evaluation des ereignisfreien Überlebens (Event-free Survival, EFS) zwischen Hochdosis (25 mg) und Niedrigdosisarm (5 mg)

E.2.2

Secondary objectives of the trial

- Evaluate safety, tolerability, and feasibility during consolidation (25 mg) and maintenance (25mg vs. 5 mg) therapy with lenalidomide.
- Evaluate the improvement of remission rates during consolidation therapy with lenalidomide and compare remissions rates during maintenance therapy with two doses of lenalidomide.
- Evaluate the quality of life of patients during consolidation and maintenance therapy with lenalidomide.

- Evaluation der Sicherheit, Verträglichkeit und Machbarkeit
- Evaluation Verbesserung der Remissionrate (RR)
- Evaluation des Gesamtüberlebens (OS)
- Evaluation der Lebensqualität (QoL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Understand and voluntarily sign an informed consent form.
- Age 18-75 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Patients with multiple myeloma who have received high-dose therapy and autologous stem cell transplantation as first-line therapy within the last 90 – 120 days and have not shown progressive disease afterwards. Patients may have received a second high-dose therapy in case of less than a vgPR or due to conditioning with intermediate dose melphalan because of an age of more than 65 years.
- Patients may have received up to 6 cycles of prior induction therapy (e.g. idarubicine, dexamethasone) and up to 2 cycles of prior mobilisation chemotherapy (e.g. cyclophosphamide). A bortezomib or thalidomide containing induction therapy is allowed. Patients may also have received prior radiation therapy. The use of lenalidomide as monotherapy or as part of a combination treatment for induction therapy is not allowed.
- Measurable levels of myeloma paraprotein in serum (>0.5 g/dL) or urine (>0.2 g/24hours) or measurable free light chains (FLC) in serum (>50 mg/l) with an abnormal FLC ratio must be documented at the time of first diagnosis.
- ECOG performance status of £ 2 at study entry.
- Laboratory and functional test results within these ranges: ANC ≥ 1,000/μL , Platelet count ≥ 100,000/μL, Total bilirubin £ 2.5 mg/dL, AST (SGOT) and ALT (SGPT) 3 x ULN, Patients with impaired renal function can be included
- The patient must be able to adhere to the pregnancy precautions.
Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast.

- Schriftliches Einverständnis
- Alter 18-75 Jahre
- Patienten mit Multiplen Myelom mit Hochdosischemotherapie und anschließender Transplantation von eigenen Blutstamm-zellen als Primärbehandlung innerhalb der letzten 90 – 120 Tage (ohne Progression). Eine zweite Hochdosistherapie im Anschluss an die erste ist erlaubt, wenn der Patient weniger als eine sehr gute partielle Remission erreicht hat oder aufgrund eines Alters von mehr als 65 Jahren eine intermediäre Melphalan-konditionierung gewählt wurde. Patienten dürfen bis Einschluss bis zu 6 Zyklen Induktions-Chemotherapie (z.B. mit Idarubicin, Dexamethason) und bis zu zwei Zyklen Mobilisations-Chemotherapie (z.B. mit Cyclophosphamid) erhalten haben. Patienten mit einer Induktions-Therapie die Bortezomib enthielt oder vorheriger Bestrahlung können eingeschlossen werden. Eine Vorbehandlung durch Thalidomid oder Lenalidomid führt zum Ausschluss des Patienten.
- Ein messbarer Verlaufsparameter muss vorhanden sein. Ein Paraprotein im Serum >0.5 g/dl) oder im Urin (>0.2 g/24Std) oder eine freie Leichtkette (FLC) im Serum (>50 mg/l) mit einem pathologischen FLC-Quotienten muss zum Zeitpunkt der Erstdiagnose vorliegen
- ECOG Allgemeinzustand < oder gleich 2
- Labor-Ergebnisse müssen innerhalb folgender Grenzwerte liegen:
- Gesamtbilirubin < oder gleich 2.5 mg/dl
- AST (SGOT) and ALT (SGPT) < oder gleich 3 x oberer
Normbereich
- Patienten mit eingeschränkter Nierenfunktion können nach
Prüfplan (Dosismodifikationen) eingeschlossen werden.
- Patienten müssen sich an die Schwangerschaftsverhütungs-massnahmen innerhalb der Studien halten. Diese sehen vor, dass weibliche Patienten einen Schwangerschaftstest vor Studienteilnahme durchführen Männliche und weibliche Patienten müssen vor, während und nach Studienteilnahme unbedingt einer sicheren Verhütungsmethode zustimmen und dies schriftlich bestätigen. Patientinnen, die während der Studie schwanger werden, müssen dem besonderen Vorgehen zu Schwangerschaften in der LenaMain-Studie schriftlich zustimmen.
- Patienten dürfen in den letzten 5 Jahren an keiner malignen Erkrankung gelitten haben, mit Ausnahme eines Basalzellkarzinoms oder eines squamösen Zellkarzinoms der Haut oder eines “carcinoma in situ” der Zervix oder der Brust.

E.4

Principal exclusion criteria

- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Any condition or laboratory abnormality which places the subject at an unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Known hypersensitivity to thalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Any prior use of thalidomide or lenalidomide.
- Known positive for HIV or active infectious hepatitis, type A, B or C.

- Alle medizinischen Zustände, laborchemischen Veränderungen oder psychiatrischen Zustände, die eine Unterzeichnung der Einverständniserklärung nicht möglich machen.
- Schwangere oder Stillende Teilnehmerinnen
- Alle laborchemischen Veränderungen, die ein nicht akzeptables Risiko für den Patienten bei einer Studienteilnahme bedeuten würden oder die Studienauswertung beeinflussen könnte.
- Bekannte Überempfindlichkeit gegenüber Thalidomid oder Thalidomidabkömmlinge
- Entwicklung eines Erythema nodosum während der Gabe von Thalidomid oder ähnlichen Medikamenten.
- Vorherige Gabe von Thalidomid oder Lenalidomid
- Aktive HIV oder Hepatitis, A, B oder C Infektion

E.5 End points

E.5.1

Primary end point(s)

- Compare the event-free survival of patients with multiple myeloma who receive two different dose levels (25 vs. 5 mg daily) of lenalidomide as maintenance therapy after first line high-dose therapy and autologous stem cell transplantation.

Evaluation und Vergleich des ereignisfreien Überlebens zwischen Hochdosis (25 mg) und Niedrigdosisarm (5 mg) bei Patienten nach Hochdosistherapie und autologer Blutstammzelltransplantation

E.5.1.1

Timepoint(s) of evaluation of this end point

disease progession

Eintritt des Krankheitsprogress

E.5.2

Secondary end point(s)

- Safety and tolerability number of SAE
- remission rate
- overall survival
- Quality of life (QoL)
- progression-free Survival 2 (PFS2)

-Sicherheit, Verträglichkeit und Machbarkeit
-Remissionsrate (RR)
-Gesamtüberleben (OS)
- Lebensqualität (QoL)
- progressionsfreies Überleben 2 (PFS2)

E.5.2.1

Timepoint(s) of evaluation of this end point

every visit until disease progression

Routinevisiten bis zur Krankheitsprogression

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Hoch- und Niedrigdosisarm

Highdose and Lowdosearm

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

Information not present in EudraCT

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

disease progression

Krankheitsprogression

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

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

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

194

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)

In the follow-up phase all subjects will be followed for survival and post anti-myeloma treatment.

Alle Patienten erhalten eine umfassende Nachsorge und eine spezielle Therapie.

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

2009-01-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-12-10

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

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Orphan Designation Number:
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