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Page 1 of 10 EU-CTR Version: 1.1.1 EU Clinical Trials Register Search for Clinical Trials Home Search About Glossary Data Quality Joining a trial Contacts EudraPharm Clinicaltrialsregister.eu Summary EudraCT Number: 2010-019173-16 Sponsor's Protocol Code Number: National Competent Authority: Clinical Trial Type: Trial Status: Date on which this record was first entered in the EudraCT database: MM5 - BfArM EEA CTA Ongoing 2010-02-23 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 A. Protocol Information A.1 Member State Concerned - BfArM A.2 EudraCT number 2010-019173-16 A.3 Full title of the trial Randomised phase III trial for previously untreated multiple myeloma to evaluate two regimens of bortezomib based induction therapy and lenalidomide consolidation followed by lenalidomide maintenance treatment A.3.1 Title of the trial for lay people, in easily understood, i.e. non-technical, language Randomisierte Phase III Studie für Patienten mit Multiplem Myelom zur Untersuchung zweier Therapieschemata einer Bortezomib-basierten Induktionsthearpie und einer Lenalidomid-Konsolidierungstherapie gefolgt von einer Erhaltungstherapie mmit Lenalidomid A.3.2 Name or abbreviated title of the trial where available A.4.1 Sponsor's protocol code number A.5.1 A.7 A.8 ISRCTN (International Standard Randomised Controlled Trial) Number Trial is part of a Paediatric Investigation Plan EMA Decision number of Paediatric Investigation Plan MM5 MM5 ISRCTN05622749 B. Sponsor Information B.Sponsor: 1 B.1.1 Name of Sponsor B.1.3.4 Country B.3.1 and B.3.2 Status of the sponsor University Hospital Heidelberg n-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.4.1 Name of organisation providing support B.4.2 Country B.4.1 Name of organisation providing support Fa. Janssen-Cilag GmbH, Neuss Fa. Celgene, München Fa. Chugai, Frankfurt am Main

Page 2 of 10 B.4.2 Country B.4.1 Name of organisation providing support B.4.2 Country The Binding Site, Schwetzingen 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 B.5.3 Address: GMMG Study Office GMMG Studiensekretariat B.5.3.1 Street Address Im Neuenheimer Feld 350 B.5.3.2 Town/ city Heidelberg B.5.3.3 Post code 69120 B.5.3.4 Country B.5.4 Telephone number 00496221568198/568015 B.5.5 Fax number 00496221561957 B.5.6 E-mail studiensekretariat.gmmg@med.uni-heidelberg.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 D.2.1.1.1 Trade name D.2.1.1.2 D.2.1.2 D.2.5 D.2.5.1 Name of the Marketing Authorisation holder Country which granted the Marketing Authorisation The IMP has been designated in this indication as an orphan drug in the Community Orphan drug designation number D.3 Description of the IMP Velcade Janssen-Cilag International NV European Union D.3.4 Pharmaceutical form Powder for solution for injection D.3.4.1 Specific paediatric formulation 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.3.10 Strength D.3.10.1 Concentration unit mg milligram(s) 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 D.3.11.2 D.3.11.3 D.3.11.3.1 Active substance of chemical origin Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) The IMP is a: Advanced Therapy IMP (ATIMP) Somatic cell therapy medicinal D.3.11.3.2 Gene therapy medical D.3.11.3.3 Tissue Engineered Product D.3.11.3.4 D.3.11.3.5 D.3.11.4 Combination ATIMP (i.e. one involving a medical device) Committee on Advanced therapies (CAT) has issued a classification for this Combination that includes a device, but does not involve an Advanced Therapy

Page 3 of 10 D.3.11.5 D.3.11.6 D.3.11.7 Radiopharmaceutical medicinal Immunological medicinal (such as vaccine, allergen, immune serum) Plasma derived medicinal D.3.11.8 Extractive medicinal D.3.11.9 D.3.11.10 Recombinant medicinal Medicinal containing genetically modified organisms D.3.11.11 Herbal medicinal D.3.11.12 Homeopathic medicinal D.3.11.13 Another type of medicinal D.3.11.13.1 Other medicinal type D.IMP: 2 D.1.2 and D.1.3 IMP Role Cytostatic drug 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 D.2.1.1.1 Trade name D.2.1.1.2 D.2.1.2 D.2.5 D.2.5.1 Name of the Marketing Authorisation holder Country which granted the Marketing Authorisation The IMP has been designated in this indication as an orphan drug in the Community Revlimid Celgene Europe Limited European Union Orphan drug designation number EU/3/03/177 D.3 Description of the IMP D.3.1 Product name Lenalidomide D.3.2 Product code CC-5013 D.3.4 Pharmaceutical form Capsule, hard D.3.4.1 Specific paediatric formulation 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 D.3.11.2 D.3.11.3 D.3.11.3.1 Active substance of chemical origin Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) The IMP is a: Advanced Therapy IMP (ATIMP) Somatic cell therapy medicinal D.3.11.3.2 Gene therapy medical D.3.11.3.3 Tissue Engineered Product D.3.11.3.4 D.3.11.3.5 D.3.11.4 D.3.11.5 Combination ATIMP (i.e. one involving a medical device) Committee on Advanced therapies (CAT) has issued a classification for this Combination that includes a device, but does not involve an Advanced Therapy Radiopharmaceutical medicinal Immunological medicinal

Page 4 of 10 D.3.11.6 D.3.11.7 (such as vaccine, allergen, immune serum) Plasma derived medicinal D.3.11.8 Extractive medicinal D.3.11.9 D.3.11.10 Recombinant medicinal Medicinal containing genetically modified organisms D.3.11.11 Herbal medicinal D.3.11.12 Homeopathic medicinal D.3.11.13 Another type of medicinal D.3.11.13.1 Other medicinal type D.IMP: 3 D.1.2 and D.1.3 IMP Role Immunomodulatory agent 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 D.2.1.1.1 Trade name D.2.1.1.2 D.2.1.2 D.2.5 D.2.5.1 Name of the Marketing Authorisation holder Country which granted the Marketing Authorisation The IMP has been designated in this indication as an orphan drug in the Community Revlimid Celgene Europe Limited European Union Orphan drug designation number EU/3/03/177 D.3 Description of the IMP D.3.1 Product name Lenalidomide D.3.2 Product code CC-5013 D.3.4 Pharmaceutical form Capsule, hard D.3.4.1 Specific paediatric formulation 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 D.3.11.2 D.3.11.3 D.3.11.3.1 Active substance of chemical origin Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) The IMP is a: Advanced Therapy IMP (ATIMP) Somatic cell therapy medicinal D.3.11.3.2 Gene therapy medical D.3.11.3.3 Tissue Engineered Product D.3.11.3.4 D.3.11.3.5 D.3.11.4 D.3.11.5 D.3.11.6 D.3.11.7 Combination ATIMP (i.e. one involving a medical device) Committee on Advanced therapies (CAT) has issued a classification for this Combination that includes a device, but does not involve an Advanced Therapy Radiopharmaceutical medicinal Immunological medicinal (such as vaccine, allergen, immune serum) Plasma derived medicinal

Page 5 of 10 D.3.11.8 Extractive medicinal D.3.11.9 D.3.11.10 Recombinant medicinal Medicinal containing genetically modified organisms D.3.11.11 Herbal medicinal D.3.11.12 Homeopathic medicinal D.3.11.13 Another type of medicinal D.3.11.13.1 Other medicinal type D.IMP: 4 D.1.2 and D.1.3 IMP Role Immunomodulatory agent 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 D.2.1.1.1 Trade name D.2.1.1.2 D.2.1.2 D.2.5 D.2.5.1 Name of the Marketing Authorisation holder Country which granted the Marketing Authorisation The IMP has been designated in this indication as an orphan drug in the Community Revlimid Celgene Europe Limited European Union Orphan drug designation number EU/3/03/177 D.3 Description of the IMP D.3.1 Product name Lenalidomide D.3.2 Product code CC-5013 D.3.4 Pharmaceutical form Capsule, hard D.3.4.1 Specific paediatric formulation 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 15 D.3.11 The IMP contains an: D.3.11.1 D.3.11.2 D.3.11.3 D.3.11.3.1 Active substance of chemical origin Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) The IMP is a: Advanced Therapy IMP (ATIMP) Somatic cell therapy medicinal D.3.11.3.2 Gene therapy medical D.3.11.3.3 Tissue Engineered Product D.3.11.3.4 D.3.11.3.5 D.3.11.4 D.3.11.5 D.3.11.6 D.3.11.7 Combination ATIMP (i.e. one involving a medical device) Committee on Advanced therapies (CAT) has issued a classification for this Combination that includes a device, but does not involve an Advanced Therapy Radiopharmaceutical medicinal Immunological medicinal (such as vaccine, allergen, immune serum) Plasma derived medicinal D.3.11.8 Extractive medicinal D.3.11.9 Recombinant medicinal

Page 6 of 10 D.3.11.10 Medicinal containing genetically modified organisms D.3.11.11 Herbal medicinal D.3.11.12 Homeopathic medicinal D.3.11.13 Another type of medicinal D.3.11.13.1 Other medicinal type D.IMP: 5 D.1.2 and D.1.3 IMP Role Immunomodulatory agent 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 D.2.1.1.1 Trade name D.2.1.1.2 D.2.1.2 D.2.5 D.2.5.1 Name of the Marketing Authorisation holder Country which granted the Marketing Authorisation The IMP has been designated in this indication as an orphan drug in the Community Revlimid Celgene Europe Limited European Union Orphan drug designation number EU/3/03/177 D.3 Description of the IMP D.3.1 Product name Lenalidomide D.3.2 Product code CC-5013 D.3.4 Pharmaceutical form Capsule, hard D.3.4.1 Specific paediatric formulation 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 D.3.11.2 D.3.11.3 D.3.11.3.1 Active substance of chemical origin Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) The IMP is a: Advanced Therapy IMP (ATIMP) Somatic cell therapy medicinal D.3.11.3.2 Gene therapy medical D.3.11.3.3 Tissue Engineered Product D.3.11.3.4 D.3.11.3.5 D.3.11.4 D.3.11.5 D.3.11.6 D.3.11.7 Combination ATIMP (i.e. one involving a medical device) Committee on Advanced therapies (CAT) has issued a classification for this Combination that includes a device, but does not involve an Advanced Therapy Radiopharmaceutical medicinal Immunological medicinal (such as vaccine, allergen, immune serum) Plasma derived medicinal D.3.11.8 Extractive medicinal D.3.11.9 D.3.11.10 Recombinant medicinal Medicinal containing genetically modified organisms D.3.11.11 Herbal medicinal

Page 7 of 10 D.3.11.12 Homeopathic medicinal D.3.11.13 Another type of medicinal D.3.11.13.1 Other medicinal type Immunomodulatory agent D.8 Information on Placebo E. General Information on the Trial E.1 Medical condition or disease under investigation E.1.1 E.1.1.1 Medical condition(s) being investigated Medical condition in easily understood language E.1.1.2 Therapeutic area MedDRA Classification E.1.3 Condition being studied is a rare disease E.2 Objective of the trial multiple myeloma (symptomatic, newly diagnosed) symptomatisches Multiples Myelom, Neudiagnose Diseases [C] - Blood and lymphatic diseases [C15] E.2.1 E.2.2 Main objective of the trial Secondary objectives of the trial 1.) Demonstration of non-inferiority of VCD induction therapy compared to PAd induction therapy with respect to response rate (very good partial remission or better; response criteria of the International Myeloma Working Group, IMWG). 2.) Determination of the best of four treatment strategies with respect to progression-free survival (PFS). The four treatment strategies are defined by PAd vs. VCD induction treatment, standard intensification therapy, lenalidomide consolidation and maintenance treatment with lenalidomide for 2 years vs. lenalidomide until CR. - overall survival rates (OS) - response rates after lenalidomide consolidation treatment - best response rates - toxicity during induction treatment, lenalidomide consolidation and maintenance treatment with respect to adverse events of CTCAE grade >= 3 E.2.3 Trial contains a sub-study E.3 Principal inclusion criteria E.4 Principal exclusion criteria newly-diagnosed symptomatic multiple myeloma ("CRAB" criteria) measurable disease age 18-70 years (both included) WHO performance status 0-2 (WHO=3 is allowed when caused by myeloma) negative pregnacy test patients must be willing and capable to use adequate contraception written informed consent hypersensitivity to any relevant medication within the trial systemic AL-amyloidosis previous chemotherapy or radiotherapy during the past 5 years severe cardiac dysfunction significant hepatic dysfunction patients known to be HIV-positive other malignancy during the past 5 years peripheral neuropathy CTC grade 2 or higher E.5 End points E.5.1 E.5.1.1 E.5.2 Primary end point(s) Timepoint(s) of evaluation of this end point Secondary end point(s) Primary endpoints: 1) Response to treatment (very good partial remission or better) after induction therapy 2) Progression free survival (i.e., time from randomisation to progression or death from any cause whichever occurs first). 1) After induction therapy 2) Progression free survival (i.e., time from randomisation to progression or death from any cause whichever occurs first). 1) Overall survival rates 2) response after lenalidomide consolidation treatment 3) best response rates 4) toxicity during induction treatment, lenalidomide consolidation and maintenance treatment with respect to adverse events CTC grade 3 or higher E.5.2.1 Timepoint(s) of evaluation of this end point E.6 and E.7 Scope of the trial any time

Page 8 of 10 E.6 Scope of the trial E.6.1 Diagnosis E.6.2 Prophylaxis E.6.3 Therapy E.6.4 Safety E.6.5 Efficacy 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 E.7.3 Therapeutic exploratory (Phase II) 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 E.8.1.2 Open E.8.1.3 Single blind E.8.1.4 Double blind E.8.1.5 Parallel group E.8.1.6 Cross over E.8.1.7 Other E.8.2 Comparator of controlled trial E.8.2.1 Other medicinal (s) E.8.2.2 Placebo E.8.2.3 Other E.8.2.3.1 Comparator description Combination and duration of treatment E.8.2.4 E.8.3 E.8.4 E.8.4.1 E.8.5 E.8.5.1 Number of treatment arms in the trial The trial involves single site in the Member State concerned The trial involves multiple sites in the Member State concerned Number of sites anticipated in Member State concerned The trial involves multiple Member States Number of sites anticipated in the EEA E.8.6 Trial involving sites outside the EEA E.8.6.1 E.8.6.2 E.8.7 E.8.8 Trial being conducted both within and outside the EEA Trial being conducted completely outside of the EEA Trial has a data monitoring committee 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 2 36 40 6 End of trial is defined as the last visit of the last subject undergoing the trial.

Page 9 of 10 E.8.9.1 E.8.9.1 E.8.9.2 E.8.9.2 E.8.9.2 In the Member State concerned months In the Member State concerned days In all countries concerned by the trial years In all countries concerned by the trial months In all countries concerned by the trial days 2 0 6 2 0 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) F.1.2.1 Number of subjects for this age range: F.1.3 Elderly (>=65 years) F.1.3.1 F.2 Gender Number of subjects for this age range: F.2.1 Female F.2.2 Male F.3 Group of trial subjects F.3.1 Healthy volunteers F.3.2 Patients F.3.3 Specific vulnerable populations F.3.3.1 F.3.3.2 Women of childbearing potential not using contraception 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 F.3.3.7 Others Subjects incapable of giving consent personally F.4 Planned number of subjects to be included 450 50 F.4.1 In the member state 444 F.4.2 For a multinational trial F.4.2.1 In the EEA 504 F.4.2.2 In the whole clinical trial 504 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) See protocol (chapter 10) G. Investigator Networks to be involved in the Trial N. Review by the Competent Authority or Ethics Committee in the country concerned N. Competent Authority Decision Authorised N. N. Date of Competent Authority Decision Ethics Committee Opinion of the trial application 2010-04-12 Favourable N. Ethics Committee Opinion: Reason

Page 10 of 10 (s) for unfavourable opinion N. Date of Ethics Committee Opinion 2010-07-08 P. End of Trial P. End of Trial Status Ongoing Legal tice EU Clinical Trials Register Service Desk: email: euctr@ema.europa.eu European Medicines Agency 1995-2011 7 Westferry Circus, Canary Wharf, London E14 4HB