A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older.

NCT00405756 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-5013-MM-0152006-001865-41
• Study Type: interventional
• Target: 459
• Locations: 20 countries
• Sites: 89

Brief Summary

The purpose of this study is to determine whether lenalidomide is safe and effective in the treatment of patients with newly diagnosed Multiple Myeloma who are 65 years of age or older.

Conditions

Newly Diagnosed Multiple Myeloma

Keywords

Newly Diagnosed Multiple Myeloma; Celgene; CC-5013; Revlimid; Lenalidomide; Melphalan; Prednisone; Elderly

Outcome Measures

Primary Outcomes (1)

• Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)

  Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry \[EBMT/IBMTR/ABMTR\] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

  up to 165 weeks

Secondary Outcomes (27)

• Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)

  Approximately week 37 (start of cycle 10) to week 165

• Kaplan Meier Estimates of Overall Survival (OS)

  up to 177 weeks

• Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)

  up to 165 weeks

• Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period

  Up to 165 weeks

• Time to First Response

  Up to 66 weeks

Study Arms (3)

MPR+R

EXPERIMENTAL

Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.

Drug: Lenalidomide: Double-blind Induction; Drug: Melphalan; Drug: Prednisone; Drug: Aspirin; Drug: Lenalidomide: Double-blind Maintenance; Drug: Lenalidomide: Open-label

MPR+p

EXPERIMENTAL

Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.

Drug: Lenalidomide: Double-blind Induction; Drug: Melphalan; Drug: Prednisone; Drug: Aspirin; Drug: Placebo; Drug: Lenalidomide: Open-label

MPp+p

OTHER

Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.

Drug: Melphalan; Drug: Prednisone; Drug: Aspirin; Drug: Placebo; Drug: Lenalidomide: Open-label

Interventions

Lenalidomide: Double-blind Induction DRUG

Double-blind Induction: the starting lenalidomide oral dosing regimen was 10 mg once daily on Days 1 through 21 of each 28 day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.

Also known as: Revlimid

MPR+R; MPR+p

Melphalan DRUG

Double-blind Induction: the starting melphalan oral dosing regimen in all 3 treatment arms was 0.18 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.

Also known as: Alkeran

MPR+R; MPR+p; MPp+p

Prednisone DRUG

Double-blind induction: the starting prednisone oral dosing regimen in all 3 treatment arms was 2 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.

MPR+R; MPR+p; MPp+p

Aspirin DRUG

Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms. Double-blind maintenance: at the investigator's discretion

MPR+R; MPR+p; MPp+p

Placebo DRUG

Double-blind induction: participants in treatment arm MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle for up to 9 cycles. Double-blind maintenance: participants in treatment arms MPR+p and MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.

MPR+p; MPp+p

Lenalidomide: Double-blind Maintenance DRUG

Single-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.

Also known as: Revlimid

MPR+R

Lenalidomide: Open-label DRUG

Any study participant who had progressive disease had the option of open-label lenalidomide up to 25 mg daily on Days 1 through 21 of each 28-day cycle.

Also known as: Revlimid

MPR+R; MPR+p; MPp+p

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Must understand and voluntarily sign an informed consent form
• Age greater than or equal to 65 years at the time of signing the informed consent
• Newly diagnosed with symptomatic multiple myeloma as defined by the 3 criteria below:
• MM diagnostic criteria (all of next 3 required)
• Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma
• Monoclonal protein present in the serum and/or urine
• Myeloma-related organ dysfunction (at least one of the following) \[C\] Calcium elevation in the blood (serum calcium \>10.5mg/dl or upper limit of normal) \[R\] Renal insufficiency (serum creatinine \>2mg/dl) \[A\] Anemia (hemoglobin \<10g/dl or 2g \< normal) \[B\] Lytic bone lesions or osteoporosis AND have measurable disease as defined by the following; IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgA multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgD multiple myeloma: Serum M-protein level greater than or equal to 0.05 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours Light chain multiple myeloma: Serum M-protein level greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level greater than or equal to 1.0g/dL or urine M-protein level greater than or equal to 200mg/24hours
• Karnofsky performance status greater than or equal to 60%.
• Able to adhere to the study visit schedule and other protocol requirements.
• Women of Childbearing potential (WCBP) must:
• a. Have a negative medically supervised pregnancy test prior to the start of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices and continues sexual abstinence.
• b Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
• Males Subjects must:
• Agree to use a condom during sexual contact with a WCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after the cessation of study therapy.
• Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

You may not qualify if:

• Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid \[i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days \[4 weeks\] of randomization\]).
• Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds experimental the ability to interpret data from the study.
• Pregnant or lactating females.
• Radiotherapy within 14 days (2 weeks) of randomization.
• Plasmapheresis within 28 days (4 weeks) of randomization.
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,500 cells/mL (1.5\*10\^9/L) Platelet count \< 75,000 cells/uL (75\*10\^9/L) for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; but platelet count \<30,000/uL for subjects in whom \>= 50% of bone marrow nucleated cells are plasma cells Haemoglobin \< 8.0 g/dL (80 g/L) Serum creatinine \> 2.5 mg/dL (221 µmol/L) Serum aspartate aminotransferase (SGOT/AST) or alanine aminotransferase (SGPT/ALT) \> 3.0 times upper limit of normal (ULN)
• Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for greater than or equal to 3 years.
• Exceptions include the following:
• Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histologic finding of prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b)
• Neuropathy of \>= grade 2 severity.
• Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis, type A, B or C.

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (98)

Hematology Oncology Clinics of Australia, Level 5, Mater Medical Centre

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital Institute of Medical and Veterinary Science

Adelaide, South Australia, 5000, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology

East Melbourne, 3006, Australia

Location

Frankston Hospital

Frankston, 3199, Australia

Location

The Alfred Hospital

Melbourne, 3141, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, 6009, Australia

Location

Princess Alexandra Hospital

Woolloongabba, 4102, Australia

Location

University Hospital Innsbruck

Innsbruck, 6020, Austria

Location

University Hospital of Salzburg St Johanns Spital

Salzburg, 5020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Wilhelminenspital

Vienna, 1160, Austria

Location

Medical University of Vienna

Vienna, A-1090, Austria

Location

Republican Scientific and Practical Centre of Radiation Medicine and Human Ecology

Homyel, 246 042, Belarus

Location

City Clinical Hospital 9

Minsk, 220116, Belarus

Location

AZ St-Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

AZ-VUB

Brussels, 1090, Belgium

Location

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liege

Liège, 4000, Belgium

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Olomouc

Olomouc, 77520, Czechia

Location

Vseobecna Fakultni Nemocnice v Praze

Prague, 128 081, Czechia

Location

Hæmatologisk afd. B Aalborg Sygehus Syd

Aalborg, 9000, Denmark

Location

Medicinsk afd. Vejle Sygehus

Vejle, 7100, Denmark

Location

CHU

Caen, 14033, France

Location

CH - Hôpital Dupuytren

Limoges, 87042, France

Location

CHU Montpellier- Hopital Lapeyronie

Montpellier, 34295, France

Location

Assistance Publique - Hôpitaux de Paris AP-HP

Paris, 75475, France

Location

CHU Purpan

Toulouse, TSA 40031-31059, France

Location

Ltd M.Zodelava Hematology Centre

Tbilisi, 0112, Georgia

Location

Institute of Hematology and Transfusiology

Tbilisi, 0177, Georgia

Location

Medizinische Klinik und Poliklinik II der Charite Campus Mitte

Berlin, 10117, Germany

Location

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, D-01307, Germany

Location

Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik

Freiburg im Breisgau, D-79106, Germany

Location

Ernst-Moritz-Arndt-Universität Greifswald

Greifswald, 17487, Germany

Location

Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V

Heidelberg, 69120, Germany

Location

Medizinische Klinik und Poliklinik II

Leipzig, D-04103, Germany

Location

Poliklinik A

Münster, 47589, Germany

Location

Medizinische Klinik - Abteilung II

Tübingen, 72076, Germany

Location

Medizinische Universitatsklinik

Ulm, 89081, Germany

Location

Medizinische Klinik und Poliklinik II des Universitatsklinikums Wurzburg

Würzburg, 97080, Germany

Location

G. GENNIMATAS General Hospital of Athens Department of Hematolgosy

Athens, 115 27, Greece

Location

General Air Force Hospital

Athens, 11525, Greece

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

Hope Directorate Haematology Oncology Service St. James Hospital

Dublin, 8, Ireland

Location

Midlands Regional

Tullamore / Co Offally, Ireland

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Hadassah University Hospital

Jerusalem, 91120, Israel

Location

Hematology Institute, Hemato-Oncology Division,Davidoff Cancer Center, Rabin MC Beilinson Hospital

Petch Tikva, 49100, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Policlinico S. Orsola

Bologna, 40138, Italy

Location

A.O.U. San Martino

Genova, 16132, Italy

Location

Dipartmento Oncologico Struttura Complessa di ematlologiaA.O. Ospedale Niguarda Ca Granda

Milan, 20162, Italy

Location

Policlinico San Matteo Universita Di Pavia

Pavia, 27100, Italy

Location

Divisione Di Ematologia Ospedale Cattedra di Ematologia

Rome, 00144, Italy

Location

Azienda Policlinico Umberto I, Universita La Sapienzadi Roma

Rome, 00161, Italy

Location

Dipartimento di Onco-Ematologia

San Giovanni Rotondo (FG), 71013, Italy

Location

Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista

Turin, 10126, Italy

Location

VU Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 GD/3000 CA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

Klinika Hematologii Samodzielny Publiczny Szpital Kliniczny Akademii

Bialystok, 15-276, Poland

Location

Institute of Internal Diseases University of Medicine

Gdansk, 80-211, Poland

Location

Oddzial Kliniczny Kliniki Hematologii

Krakow, 31-501, Poland

Location

Uniwersytet Medyczny w Lodzi

Lodz, 93-509, Poland

Location

University School of Medicine

Lublin, 20-290, Poland

Location

Akademia Medyczna w Warszawie Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, 02-097, Poland

Location

Burdenko Central Military Clinical Hospital

Moscow, 105229, Russia

Location

Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl

Moscow, 115678, Russia

Location

Moscow Regional Research Institute n.a. Vladimirsky

Moscow, 129110, Russia

Location

Novosibirsk State Regional Clinical Hospital

Novosibirsk, 630087, Russia

Location

Medical Radiological Research Center RAMS

Obninsk, 249036, Russia

Location

St. Petersburg Research Institute of Hematology and Blood Transfusion

Saint Petersburg, 191024, Russia

Location

Samara Regional Clinical Hospital

Samara, 443095, Russia

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

Hospital Universitaro Puerta del MarServicio de Hematologia

Cadiz, 11009, Spain

Location

Hospital Universitario de la Princessa

Madrid, 28006, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Virgen del Rocio Servicio de Hematologia

Seville, 41013, Spain

Location

Medicinkliniken

Borås, 501 82, Sweden

Location

Medicinska kliniken

Malmo, 20502, Sweden

Location

UniversitatsSpital ZurichKlinik fur Onkologie

Zurich, CH-8091, Switzerland

Location

Ankara University

Ankara, 06620, Turkey (Türkiye)

Location

Marmara School of Medicine

Istanbul, 34662, Turkey (Türkiye)

Location

Ege University Medical School

Izmir, 35100, Turkey (Türkiye)

Location

Cherkassy Regional Oncology Center

Cherkassy, 18009, Ukraine

Location

Dnepropetrovsk City Clinical Hospital 4

Dnipro, 49044, Ukraine

Location

Institute of Urgent and Recovery Surgery

Donetsk, 83047, Ukraine

Location

Institute of Hematology and Transfusiology of the UAMS Department of blood diseases

Kiev, 04060, Ukraine

Location

Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine

Lviv, Ukraine

Location

Zhitomir Regional Clinical Hospital

Zhytomyr, 10003, Ukraine

Location

Monklands Hospital

Aidrie, ML6 0JS, United Kingdom

Location

St James's University Hospital

Leeds, LS7 9TF, United Kingdom

Location

University College London Hospitals Cancer Clinical Trials Unitist FloorCentral wing

London, NW1 2PG, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Christie NHS Trust Hospital

Manchester, M20 4BX, United Kingdom

Location

Related Publications (3)

• Dimopoulos MA, Delforge M, Hajek R, Kropff M, Petrucci MT, Lewis P, Nixon A, Zhang J, Mei J, Palumbo A. Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial. Haematologica. 2013 May;98(5):784-8. doi: 10.3324/haematol.2012.074534. Epub 2012 Dec 14.

  PMID: 23242595 RESULT

• Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Blade J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. doi: 10.1056/NEJMoa1112704.

  PMID: 22571200 RESULT

• Dimopoulos MA, Petrucci MT, Foa R, Catalano J, Kropff M, Terpos E, Zhang J, Grote L, Jacques C, Palumbo A; MM-015 Investigators. Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point. Haematologica. 2015 Aug;100(8):e328-30. doi: 10.3324/haematol.2014.120790. Epub 2015 Apr 3. No abstract available.

  PMID: 25840600 DERIVED

MeSH Terms

Interventions

Lenalidomide; Melphalan; Prednisone; Aspirin

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Antonio Palumbo, M.D.

  Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2006
• First Posted: November 30, 2006
• Study Start: January 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: April 1, 2016
• Last Updated: January 11, 2017
• Results First Posted: May 11, 2012

Record last verified: 2016-11

Locations

UA (6); SE (2); DK (2); NL (4); BE (2); FR (5); CZ (4); ES (5); CH (1); GR (3); GB (5); IT (8); DE (10); IL (4); GE (2); IE (2); PL (6); AU (8); TU (3); RU (7)