A Study of Lenalidomide Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene ( Celgene Corporation )
ClinicalTrials.gov Identifier:
NCT00424047
First received: January 17, 2007
Last updated: March 3, 2015
Last verified: March 2015
  Purpose
The study compared the efficacy of oral lenalidomide in combination with oral pulse high-dose dexamethasone to that of placebo and oral high-dose pulse dexamethasone as treatment for participants with relapsed or refractory multiple myeloma.

Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Parallel-group, Double-blind, Placebo Controlled Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma.

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Kaplan-Meier Estimate of Time to Tumor Progression (TTP) [ Time Frame: From randomization up to cut-off date of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

  • Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008) [ Time Frame: From randomization up to cut-off date of 02 March 2008; up to 51 months ] [ Designated as safety issue: No ]
    Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.


Secondary Outcome Measures:
  • Kaplan-Meier Estimate of Overall Survival (OS) [ Time Frame: Randomization to data cut off of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    OS was calculated as the time from randomization to death from any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

  • Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008) [ Time Frame: Randomization to data cut off of 02 March 2008; up to 51 months ] [ Designated as safety issue: No ]
    OS was calculated as the time from randomization to death from any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

  • Summary of Myeloma Response Rates Based on Best Response Assessment [ Time Frame: Randomization to 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma.

  • Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) [ Time Frame: Randomization to data cut-off of 02 Mar 2008; up to 51 months ] [ Designated as safety issue: No ]
    Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma.

  • Number of Participants With Adverse Events (AE) [ Time Frame: From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 25 June 2013; up to 90 months ] [ Designated as safety issue: Yes ]

    An AE is any sign, symptom, illness, or diagnosis that appears or worsens during the course of the study. Treatment-emergent AEs (TEAEs) are any AE occurring or worsening on or after the first treatment of the study drug and within 30 days after the last cycle end date of study drug. A serious AE = any AE which results in death; is life-threatening; requires or prolongs existing inpatient hospitalization; results in persistent or significant disability is a congenital anomaly/birth defect; constitutes an important medical event.

    The severity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE, Version 2.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.


  • Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone) [ Time Frame: Up to unblinding data cut off of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    Time from randomization to the date of the first occurrence of a symptomatic SRE (clinical need for radiotherapy or surgery to bone).

  • Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale [ Time Frame: Randomization to cut off date of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented.

  • Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) [ Time Frame: Randomization to cut off date of 02 March 2008; up to 51 months ] [ Designated as safety issue: No ]
    The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented.


Enrollment: 351
Study Start Date: September 2003
Study Completion Date: November 2013
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide plus dexamethasone
Lenalidomide was administered at a dose of 25 mg by mouth daily for 21 days every 28 days. The participant also received a matching placebo identical in appearance to the lenalidomide capsule daily on Day 22 to Day 28 of each 28 cycle. Oral pulse dexamethasone was administered at a dose of 40mg daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4 until disease progression. Beginning with Cycle 5, the oral dexamethasone dosing schedule was reduced to 40mg daily for Days 1-4 every 28 days.
Drug: Lenalidomide
25 mg Lenalidomide administered by mouth daily on Days 1-21 of each 28-day treatment cycle until disease progression.
Other Names:
  • Revlimid®
  • CC-5013
Drug: Dexamethasone
Oral pulse dexamethasone for oral administration
Other Name: Decadron
Drug: Placebo
Other Name: A matching placebo capsule
Experimental: Dexamethasone plus placebo
Oral pulse dexamethasone was administered at a dose of 40mg by mouth daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4. Beginning with Cycle 5, the oral dexamethasone dosing schedule was reduced to 40mg daily for Days 1-4 every 28 days until disease progression. In addition, oral placebo capsules were administered on Days 1 to 28 of each 28 cycle.
Drug: Dexamethasone
Oral pulse dexamethasone for oral administration
Other Name: Decadron
Drug: Placebo
Other Name: A matching placebo capsule

Detailed Description:

The study was initiated in 2003 and enrolled a total of 351 participants. The study was unblinded starting on 03 August 2005 after a preplanned interim analysis demonstrated a highly significant treatment benefit in favor of the lenalidomide/dexamethasone combination based on results for the primary endpoint, time to progression (TTP). In March 2008, the specified number of at least 194 death events needed for full statistical power of the overall survival (OS) analysis was reached.

At the time of the 02 March 2008 cutoff date, there were still 29 participants in active treatment in Europe (Austria, Belgium, France, Italy, Poland, Spain and Ukraine) and Israel. Only safety data were collected for these participants beyond the 02 March 2008 cutoff date. The last visit for the last patient occurred on 25 June 2013.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior or current diagnosis Durie-Salmon stage II or III multiple myeloma.
  • Measurable levels of myeloma paraprotein in serum or urine (24-hour collection sample).
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2
  • Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days of starting study drug

Exclusion Criteria:

  • Prior development of disease progression during high-dose dexamethasone containing therapy
  • Pregnant or lactating females
  • The development of a desquamating rash while taking thalidomide
  • Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment
  • Laboratory abnormalities: Absolute neutrophil count less than 1,000 cells/mm^3
  • Laboratory abnormalities: Platelet count < 75,000/mm^3
  • Laboratory abnormalities: Serum creatinine > 2.5 mg/dL
  • Laboratory abnormalities: Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/Alanine aminotransferase (ALT) > 3.0 x upper limit of normal
  • Laboratory abnormalities: Serum total bilirubin > 2.0 mg/dL
  • Prior history of malignancies other than multiple myeloma unless the subject has been free of the disease for ≥ 3 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424047

  Hide Study Locations
Locations
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Australia, Victoria
Peter MacCallum Cancer Centre Divsion of Haematology/Medical Oncology
East Melbourne, Victoria, Australia, 3006
The Alfred Hospital
Prahran, Victoria, Australia, 3121
Border Medical Oncology
Wodonga, Victoria, Australia, 3690
Australia
Box Hill Hospital
Box Hill, Australia, VIC 3128
Frankston Hospital Oncology Research
Frankston, Australia, VIC 3199
Royal Brisbane Hospital
Herston, Australia, QLD4029
The Royal Melbourne Hospital
Parkville, Australia, 3050
Mater Public Hospital
South Brisbane, Australia, QLD 4101
Austria
University Hospital of Salzburg St Johanns Spital
Salzburg, Austria, A -5020
Wilhelminenspital
Vienna, Austria, 1160
Belgium
CHU Saint-Luc
Brussel, Belgium, 1200
UZ Gasthuisberg
Leuven, Belgium, 3000
France
Centre Hospitalier Lyon Sud
Chemin Grand Revoyet, France, 69495 Pierre Benite cedex
Hopital Claude Huriez
Lille, France, 59037
Centre Hospitalier Hotel-Dieu
Nantes, France
Hopital Saint-Loius
Paris, France, 75010
Chu de Bordeaux Groupe Hospitalier Sud
Pessac, France, 33640
CHU Purpan
Toulouse cedex 9, France, TSA 40031-31059
CHU Nancy - Hopital Brabois
Vandoeuvre, France, 54511
Germany
Universitaetsklinikum Charite
Berlin, Germany, 13125
Universitatsklinik ChariteMedizinische Fakultaet der HumboldtUniversitaet zu Berlin
Berlin, Germany, 13353
Universitaetsklinikum Dusseldorf Klinik fuer Haematologie
Dusseldorf, Germany, 40225
Universitaetsklinkum Erlangen
Erlangen, Germany, 91054
Klininkum der Johann-Wolfgang-Goethe-Universtat
Frankfurt am Main, Germany, 60590
Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V
Heidelberg, Germany, 69120
Universitatsklinik Muenster Medizinische Klinik A
Muenster, Germany, 48129
Klinikum der Univeristact Muenchen
Munchen, Germany, 80336
Universitaetsklinikum Tuebingen
Tubingen, Germany, 72076
Greece
"Alexandras" General Hospital of Athens
Athens, Greece, 11538
Ireland
University Hospital GalwayHaematology Department
Galway, Co. Galway, Ireland
Belfast City HospitalHaematology Department
Belfast, Ireland, BT9 7AB
Hope Directorate Haematology Oncology Service St. James Hospital
Dublin 8, Ireland
MidWestern Regional Hospital
Limerick, Ireland
Israel
Rambam Medical Center
Haifa, Israel, 31096
Hadassah University Hospital
Jerusalem, Israel
Tel Aviv Sourasky Medical Center Department of Hematology
Tel Aviv, Israel, 64239
The Chaim Sheba Medical Center
Tel Hashomer, Israel, 52621
Italy
Policlinico Sant'Orsola-Malpighi
Bologna, Italy, 40138
Azienda Ospedaliera San Martino
Genova, Italy, 16132
Ospedale Niguarda Ca Granda
Milano, Italy, 20162
Policlinico San Matteo
Pavia, Italy, 27100
Univerita La Sapien
Roma, Italy, 00161
Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
Torio, Italy, 10126
Policlinico Universitario a Gesttione diretta di Udine
Udine, Italy, 33100
Poland
Institute of Internal Diseases University of Medicine
Gdansk, Poland, 80-211
University School of Medicine
Lublin, Poland, 20-290
Institute of Haematology and Blood Transfusion
Warsaw, Poland, 00-957
Spain
Hospital Clinic
Barcelona, Spain, 08036
Hospital Universitario de la Princessa
Madrid, Spain, 28006
Hospital Doce de Octubre
Madrid, Spain, 28041
Clinica Universitaria de Navarra
Pamplona, Spain, 31080
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universtario Marques de Valdecilla
Santander, Spain, 39008
Sweden
Sahlgrenska University Hospital Department of Hematology and Coagulation
Goteborg, Sweden, S-413 45
Switzerland
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Switzerland, 1011
Kantonsspital St. Gallen
St. Gallen, Switzerland
Universitätsspital Zürich
Zürich, Switzerland, 8091
Ukraine
Cherkassy Regional Oncology Center
Cherkassy, Ukraine, 18009
Dnepropetrovsk City Clinical Hospital #4
Dnepropetrovsk, Ukraine, 49044
Kiev Bone Marrow Transplantation Center Bone Marrow Department
Kiev, Ukraine, 03115
Institute of Hematology and Transfusiology of the UAMS Department of blood diseases
Kiev, Ukraine, 04060
Institute of Blood Pathology and Transfusion Medicine of the UAMS
Lviv, Ukraine, 79044
Institute of Blood Pathology and Transfusion Medicine of the UAMS Hematology Department
Lvov, Ukraine, 79044
Odess Regional Clinical Hospital
Odessa, Ukraine, 65025
Zhitomir Regional Clinical Hospital
Zhitomir, Ukraine, 10003
United Kingdom
University College Hospital Trust
London, Bloomsbury, United Kingdom, WC1E 6AU
Bristol Haematology and Oncology Centre
Bristol, United Kingdom, BS2 8ED
Haematology Dept, 4th Floor Thomas Guy House
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Robert Knight, MD Celgene Corporation
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00424047     History of Changes
Other Study ID Numbers: CC-5013-MM-010 
Study First Received: January 17, 2007
Results First Received: February 13, 2015
Last Updated: March 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene:
Multiple Myeloma
Celgene
Revlimid
CC-5013

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on August 25, 2016