Newly Diagnosed Multiple MyelomaPhase 3NCT00405756
A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older.
A Phase 3 study testing Lenalidomide: Double-blind Induction, Melphalan and Prednisone in people with Newly Diagnosed Multiple Myeloma, run by Celgene Corporation at 98 sites in 22 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Newly Diagnosed Multiple Myeloma
- What is being tested?
- Lenalidomide: Double-blind Induction, Melphalan and Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 459 participants
- Where
- 98 sitesin 22 countries
- Study dates
- Jan 2007to Apr 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
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- 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:
- 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.
- All subjects must
- Have an understanding that the study drug could have potential teratogenic risk.
- Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
- Agree not to share study medication with another person.
- All patients must be counseled about pregnancy precautions and risks of fetal exposure.
- Female Subjects:
- Females of childbearing potential (FCBP) with regular cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study discontinuation, and at day 28 following discontinuation from the study. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 28 following discontinuation from the study.
- In addition to the required pregnancy testing, the Investigator must confirm with FCBP that she is continuing to use two reliable methods of birth control at each visit. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood.
- Pregnancy testing and counseling must be performed if a subject misses her period or if her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be discontinued during this evaluation.
- Females must agree to abstain from breastfeeding during study participation and for at least 28 days after the discontinuation from the study.
- Male Subjects:
- Counseling about the requirement for latex condom use during sexual contact with females of childbearing potential and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood, sperm, or semen.
- If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a study subject during study participation, study drug must be immediately discontinued.
Who cannot join
- 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:
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- Absolute neutrophil count (ANC) < 1,500 cells/mL (1.510^9/L) Platelet count < 75,000 cells/uL (7510^9/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.
Trial locations and contacts
98 sites in 22 countries.
98 sites in 22 countries
Germany10 sites
Medizinische Klinik und Poliklinik II der Charite Campus Mitte
Berlin, 10117
Universitatsklinikum Carl Gustav Carus an der TU Dresden
Dresden, D-01307
Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik
Freiburg im Breisgau, D-79106
Ernst-Moritz-Arndt-Universität Greifswald
Greifswald, 17487
Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V
Heidelberg, 69120
Medizinische Klinik und Poliklinik II
Leipzig, D-04103
Poliklinik A
Münster, 47589
Medizinische Klinik - Abteilung II
Tübingen, 72076
Medizinische Universitatsklinik
Ulm, 89081
Medizinische Klinik und Poliklinik II des Universitatsklinikums Wurzburg
Würzburg, 97080
Australia8 sites
Royal Adelaide Hospital Institute of Medical and Veterinary Science
Adelaide, South Australia, 5000
Royal Prince Alfred Hospital
Camperdown, 2050
Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology
East Melbourne, 3006
Frankston Hospital
Frankston, 3199
The Alfred Hospital
Melbourne, 3141
Sir Charles Gairdner Hospital
Nedlands, 6009
Hematology Oncology Clinics of Australia, Level 5, Mater Medical Centre
South Brisbane, Queensland, 4101
Princess Alexandra Hospital
Woolloongabba, 4102
Italy8 sites
Policlinico S. Orsola
Bologna, 40138
A.O.U. San Martino
Genova, 16132
Dipartmento Oncologico Struttura Complessa di ematlologiaA.O. Ospedale Niguarda Ca Granda
Milan, 20162
Policlinico San Matteo Universita Di Pavia
Pavia, 27100
Divisione Di Ematologia Ospedale Cattedra di Ematologia
Rome, 00144
Azienda Policlinico Umberto I, Universita La Sapienzadi Roma
Rome, 00161
Dipartimento di Onco-Ematologia
San Giovanni Rotondo (FG), 71013
Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
Turin, 10126
Russia7 sites
Burdenko Central Military Clinical Hospital
Moscow, 105229
Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl
Moscow, 115678
Moscow Regional Research Institute n.a. Vladimirsky
Moscow, 129110
Novosibirsk State Regional Clinical Hospital
Novosibirsk, 630087
Medical Radiological Research Center RAMS
Obninsk, 249036
St. Petersburg Research Institute of Hematology and Blood Transfusion
Saint Petersburg, 191024
Samara Regional Clinical Hospital
Samara, 443095
Poland6 sites
Klinika Hematologii Samodzielny Publiczny Szpital Kliniczny Akademii
Bialystok, 15-276
Institute of Internal Diseases University of Medicine
Gdansk, 80-211
Oddzial Kliniczny Kliniki Hematologii
Krakow, 31-501
Uniwersytet Medyczny w Lodzi
Lodz, 93-509
University School of Medicine
Lublin, 20-290
Akademia Medyczna w Warszawie Samodzielny Publiczny Centralny Szpital Kliniczny
Warsaw, 02-097
Ukraine6 sites
Cherkassy Regional Oncology Center
Cherkassy, 18009
Dnepropetrovsk City Clinical Hospital 4
Dnipro, 49044
Institute of Urgent and Recovery Surgery
Donetsk, 83047
Institute of Hematology and Transfusiology of the UAMS Department of blood diseases
Kiev, 04060
Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine
Lviv
Zhitomir Regional Clinical Hospital
Zhytomyr, 10003
Austria5 sites
University Hospital Innsbruck
Innsbruck, 6020
University Hospital of Salzburg St Johanns Spital
Salzburg, 5020
Medical University of Vienna
Vienna, 1090
Wilhelminenspital
Vienna, 1160
Medical University of Vienna
Vienna, A-1090
France5 sites
CHU
Caen, 14033
CH - Hôpital Dupuytren
Limoges, 87042
CHU Montpellier- Hopital Lapeyronie
Montpellier, 34295
Assistance Publique - Hôpitaux de Paris AP-HP
Paris, 75475
CHU Purpan
Toulouse, TSA 40031-31059
Spain5 sites
Hospital Clinic
Barcelona, 08036
Hospital Universitaro Puerta del MarServicio de Hematologia
Cadiz, 11009
Hospital Universitario de la Princessa
Madrid, 28006
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Virgen del Rocio Servicio de Hematologia
Seville, 41013
United Kingdom5 sites
Monklands Hospital
Aidrie, ML6 0JS
St James's University Hospital
Leeds, LS7 9TF
University College London Hospitals Cancer Clinical Trials Unitist FloorCentral wing
London, NW1 2PG
Kings College Hospital
London, SE5 9RS
Christie NHS Trust Hospital
Manchester, M20 4BX
Belgium4 sites
AZ St-Jan Brugge Oostende AV
Bruges, 8000
AZ-VUB
Brussels, 1090
UZ Gasthuisberg
Leuven, 3000
Centre Hospitalier Universitaire de Liege
Liège, 4000
Czechia4 sites
Fakultni nemocnice Brno
Brno, 625 00
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Fakultni Nemocnice Olomouc
Olomouc, 77520
Vseobecna Fakultni Nemocnice v Praze
Prague, 128 081
Israel4 sites
Rambam Medical Center
Haifa, 31096
Hadassah University Hospital
Jerusalem, 91120
Hematology Institute, Hemato-Oncology Division,Davidoff Cancer Center, Rabin MC Beilinson Hospital
Petch Tikva, 49100
The Chaim Sheba Medical Center
Tel HaShomer, 52621
Netherlands4 sites
VU Medical Center
Amsterdam, 1081 HV
Erasmus Medical Center
Rotterdam, 3015 GD/3000 CA
Erasmus Medisch Centrum
Rotterdam, 3015 GD
Universitair Medisch Centrum Utrecht
Utrecht
Greece3 sites
G. GENNIMATAS General Hospital of Athens Department of Hematolgosy
Athens, 115 27
General Air Force Hospital
Athens, 11525
Alexandra General Hospital of Athens
Athens, 11528
Turkey (Türkiye)3 sites
Ankara University
Ankara, 06620
Marmara School of Medicine
Istanbul, 34662
Ege University Medical School
Izmir, 35100
Belarus2 sites
Republican Scientific and Practical Centre of Radiation Medicine and Human Ecology
Homyel, 246 042
City Clinical Hospital 9
Minsk, 220116
Denmark2 sites
Hæmatologisk afd. B Aalborg Sygehus Syd
Aalborg, 9000
Medicinsk afd. Vejle Sygehus
Vejle, 7100
Georgia2 sites
Ltd M.Zodelava Hematology Centre
Tbilisi, 0112
Institute of Hematology and Transfusiology
Tbilisi, 0177
Ireland2 sites
Hope Directorate Haematology Oncology Service St. James Hospital
Dublin, 8
Midlands Regional
Tullamore / Co Offally
Switzerland1 site
UniversitatsSpital ZurichKlinik fur Onkologie
Zurich, CH-8091
About this study
Official title: A Phase III, Multicentre, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Parallel Group Study To Determine The Efficacy And Safety Of Lenalidomde (Revlimid®) In Combination With Melphalan And Prednisone Versus Placebo Plus Melphalan And Prednisone In Subjects With Newly Diagnosed Multiple Myeloma Who Are 65 Years Of Age Or Older
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.
Read the detailed description
The three phases for the study as originally defined and as represented in the results of 11 May 2010 are:
Double-blind Treatment Phase: Induction Melphalan/prednisone and lenalidomide 10 mg (MPR) (2 treatment arms), or melphalan/prednisone and placebo (MPp) (1 treatment arm) for up to 9 cycles. If disease progression, subjects have the option to enter into the Open-Label Extension Phase. There is also an option to enter into the Follow-Up Phase. If the disease has not progressed, subject can continue on blinded therapy into Maintenance.
Double-blind Treatment Phase: Maintenance One MPR treatment arm (MPR+R) will continue taking lenalidomide 10 mg in Maintenance. The other MPR treatment arm (MPR+p) will take placebo in Maintenance. The MP p treatment arm will take placebo in Maintenance (MPp+p). If disease progression, subjects have the option to enter the Open-Label Extension Phase to obtain treatment with lenalidomide, or to enter into the Follow-up Phase.
Open-label Extension Phase:
Treatment consists of oral lenalidomide (up to 25 mg) with or without dexamethasone until disease progression or treatment is discontinued for any reason until all study subjects are followed for at least 5 years from the date of randomization or have died. Subjects who discontinue from the Open-Label Extension Phase prior to completing a total of 5 years in the study will enter the Follow-up Phase.
Follow-up Phase:
Subjects are followed for overall survival and subsequent anti-myeloma treatment regimens until all subjects in this study are followed for at least 5 years from randomization or have died.
The pre-planned interim analysis for the Independent Data Monitoring Committee (IDMC) showed that the difference in progression-free survival (PFS) between treatment arms MPR+R and MPp+p (the defined primary comparative analysis for this study) surpassed the pre-specified O'Brien-Fleming boundary for superiority. The IDMC recommended the release of this information to the sponsor and also recommended that all patient and physician study participants receive information concerning the full findings of the MM-015 interim analysis. Therefore, due to these recommendations from the IDMC, treatment-arm codes were sent to the clinical trial centers to unblind the treatment arms of their study subjects once the amended protocol was reviewed and approved by the respective country Health Authorities and Ethics Committees. Subject participation in the MM-015 study continued after unblinding to obtain long-term data for all study endpoints, including overall survival.
When the study was unblinded, subjects still on protocol therapy had completed the Double-Blind Induction, and were on monotherapy in Double-Blind Maintenance. Subjects in arm MPR+R continued their monotherapy on lenalidomide. Subjects in arms MPR+p and MPp+p discontinued their placebo monotherapy and went into an observation period in which no antimyeloma therapy was taken. If disease progressed for any subject, the investigator had the option of entering the subject in Open Label Extension Phase to receive lenalidomide therapy (up to 25 mg daily) or the Follow-up Phase. All subjects were to be followed for at least 5 years from the start of the study.
- Conditions
- Newly Diagnosed Multiple Myeloma
- Being tested
- Lenalidomide: Double-blind Induction, Melphalan, Prednisone, Aspirin, Placebo
- Keywords
- Newly Diagnosed Multiple Myeloma, Celgene, CC-5013, Revlimid, Lenalidomide, Melphalan, Prednisone, Elderly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenalidomide: Double-blind InductionDrug
Also called Revlimid
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.
MelphalanDrug
Also called Alkeran
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.
PrednisoneDrug
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.
AspirinDrug
Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms.
Double-blind maintenance: at the investigator's discretion
PlaceboDrug
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.
Lenalidomide: Double-blind MaintenanceDrug
Also called Revlimid
Single-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.
Lenalidomide: Open-labelDrug
Also called Revlimid
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Melphalan; Drug: Prednisone; Drug: Aspirin; Drug: Placebo; Drug: Lenalidomide: Open-label |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period 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.
Measured: Approximately week 37 (start of cycle 10) to week 165
Kaplan Meier Estimates of Overall Survival (OS)
Data as of 11 May 2010 cutoff. Overall survival (OS) was defined as the time between randomization and death. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who were lost to follow-up prior to the end of the trial, or who were withdrawn from the trial, were censored at the time of last contact. Participants who were still being treated were censored at the last available date available, or clinical cut-off date, if it was earlier.
Measured: up to 177 weeks
Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. 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.
Measured: up to 165 weeks
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period
Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE).
Measured: Up to 165 weeks
Time to First Response
Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria.
Measured: Up to 66 weeks
Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)
Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. 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.
Measured: Up to 149 weeks
Kaplan Meier Estimates for Time to Next Antimyeloma Therapy
Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.
Measured: Up to 168 weeks
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period
Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. Dose reduction includes reduction with or without interruption.
Measured: Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale
Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image.
Measured: Baseline (Day 0), Months 4, 7, 10, 13, 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2006 (estimated)
- Study startJan 2007
- Primary completionNov 2009
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Newly Diagnosed Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 459 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antonio Palumbo, M.D., Principal investigator, Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00405756
- Sponsor's protocol ID
- CC-5013-MM-015
- Other IDs
- 2006-001865-41
- Status last verified
- Nov 2016
- First submitted
- 29 Nov 2006
- Last updated
- 11 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23242595Palumbo 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.
PubMed 22571200Dimopoulos 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.
PubMed 25840600
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicentre, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Parallel Group Study To Determine The Efficacy And Safety Of Lenalidomde (Revlimid®) In Combination With Melphalan And Prednisone Versus Placebo Plus Melphalan And Prednisone In Subjects With Newly Diagnosed Multiple Myeloma Who Are 65 Years Of Age Or Older
- ClinicalTrials.gov ID
- NCT00405756
- Acronym / sponsor ID
- CC-5013-MM-015
- Conditions
- Newly Diagnosed Multiple Myeloma
- Keywords
- Newly Diagnosed Multiple Myeloma, Celgene, CC-5013, Revlimid, Lenalidomide, Melphalan, Prednisone, Elderly
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 459 participants (actual)
- Lead sponsor
- Celgene CorporationIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Nov 2009 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 30 Nov 2006 (estimated)
- Results
- Posted 11 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The three phases for the study as originally defined and as represented in the results of 11 May 2010 are:
Double-blind Treatment Phase: Induction Melphalan/prednisone and lenalidomide 10 mg (MPR) (2 treatment arms), or melphalan/prednisone and placebo (MPp) (1 treatment arm) for up to 9 cycles. If disease progression, subjects have the option to enter into the Open-Label Extension Phase. There is also an option to enter into the Follow-Up Phase. If the disease has not progressed, subject can continue on blinded therapy into Maintenance.
Double-blind Treatment Phase: Maintenance One MPR treatment arm (MPR+R) will continue taking lenalidomide 10 mg in Maintenance. The other MPR treatment arm (MPR+p) will take placebo in Maintenance. The MP p treatment arm will take placebo in Maintenance (MPp+p). If disease progression, subjects have the option to enter the Open-Label Extension Phase to obtain treatment with lenalidomide, or to enter into the Follow-up Phase.
Open-label Extension Phase:
Treatment consists of oral lenalidomide (up to 25 mg) with or without dexamethasone until disease progression or treatment is discontinued for any reason until all study subjects are followed for at least 5 years from the date of randomization or have died. Subjects who discontinue from the Open-Label Extension Phase prior to completing a total of 5 years in the study will enter the Follow-up Phase.
Follow-up Phase:
Subjects are followed for overall survival and subsequent anti-myeloma treatment regimens until all subjects in this study are followed for at least 5 years from randomization or have died.
The pre-planned interim analysis for the Independent Data Monitoring Committee (IDMC) showed that the difference in progression-free survival (PFS) between treatment arms MPR+R and MPp+p (the defined primary comparative analysis for this study) surpassed the pre-specified O'Brien-Fleming boundary for superiority. The IDMC recommended the release of this information to the sponsor and also recommended that all patient and physician study participants receive information concerning the full findings of the MM-015 interim analysis. Therefore, due to these recommendations from the IDMC, treatment-arm codes were sent to the clinical trial centers to unblind the treatment arms of their study subjects once the amended protocol was reviewed and approved by the respective country Health Authorities and Ethics Committees. Subject participation in the MM-015 study continued after unblinding to obtain long-term data for all study endpoints, including overall survival.
When the study was unblinded, subjects still on protocol therapy had completed the Double-Blind Induction, and were on monotherapy in Double-Blind Maintenance. Subjects in arm MPR+R continued their monotherapy on lenalidomide. Subjects in arms MPR+p and MPp+p discontinued their placebo monotherapy and went into an observation period in which no antimyeloma therapy was taken. If disease progressed for any subject, the investigator had the option of entering the subject in Open Label Extension Phase to receive lenalidomide therapy (up to 25 mg daily) or the Follow-up Phase. All subjects were to be followed for at least 5 years from the start of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MPR+R | Experimental | Drug: Lenalidomide: Double-blind Induction, Drug: Melphalan, Drug: Prednisone, Drug: Aspirin, Drug: Lenalidomide: Double-blind Maintenance, Drug: Lenalidomide: Open-labelDouble-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. |
| MPR+p | Experimental | Drug: Lenalidomide: Double-blind Induction, Drug: Melphalan, Drug: Prednisone, Drug: Aspirin, Drug: Placebo, Drug: Lenalidomide: Open-labelDouble-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. |
| MPp+p | Other | Drug: Melphalan, Drug: Prednisone, Drug: Aspirin, Drug: Placebo, Drug: Lenalidomide: Open-labelDouble-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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (28 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lenalidomide: Double-blind InductionAlso: RevlimidDouble-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. | Drug | MPR+R, MPR+p |
| MelphalanAlso: AlkeranDouble-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. | Drug | MPR+R, MPR+p, MPp+p |
| PrednisoneDouble-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. | Drug | MPR+R, MPR+p, MPp+p |
| AspirinDouble-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms. Double-blind maintenance: at the investigator's discretion | Drug | MPR+R, MPR+p, MPp+p |
| PlaceboDouble-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. | Drug | MPR+p, MPp+p |
| Lenalidomide: Double-blind MaintenanceAlso: RevlimidSingle-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression. | Drug | MPR+R |
| Lenalidomide: Open-labelAlso: RevlimidAny 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. | Drug | MPR+R, MPR+p, MPp+p |
Primary outcome
Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Time frame: up to 165 weeks
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.
27 secondary outcomes
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)
Time frame: Approximately week 37 (start of cycle 10) to week 165
Kaplan Meier Estimates of Overall Survival (OS)
Time frame: up to 177 weeks
Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Time frame: up to 165 weeks
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period
Time frame: Up to 165 weeks
Time to First Response
Time frame: Up to 66 weeks
Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)
Time frame: Up to 149 weeks
Kaplan Meier Estimates for Time to Next Antimyeloma Therapy
Time frame: Up to 168 weeks
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period
Time frame: Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale
Time frame: Baseline (Day 0), Months 4, 7, 10, 13, 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23242595Dimopoulos 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.
- Results publication: PubMed 22571200Palumbo 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.
- Derived from this study: PubMed 25840600Dimopoulos 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Palumbo, M.D. principal investigator
Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
98 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lenalidomide: Double-blind Induction, Melphalan and Prednisone in people with Newly Diagnosed Multiple Myeloma, run by Celgene Corporation at 98 sites in 22 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 98 sites in Germany, Australia, Italy, Russia, Poland and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC) (time frame: up to 165 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00405756, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2017.