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

January 17, 2007
March 3, 2015
September 2003
August 2005   (final data collection date for primary outcome measure)
  • 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.
Not Provided
Complete list of historical versions of study NCT00424047 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
A Study of Lenalidomide Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Patients With Multiple Myeloma
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.
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Multiple Myeloma
  • 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: 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.
    Interventions:
    • Drug: Lenalidomide
    • Drug: Dexamethasone
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Dexamethasone
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
351
November 2013
August 2005   (final data collection date for primary outcome measure)

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.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   France,   Germany,   Greece,   Ireland,   Israel,   Italy,   Poland,   Spain,   Sweden,   Switzerland,   Ukraine,   United Kingdom
 
NCT00424047
CC-5013-MM-010
Yes
Not Provided
Not Provided
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Robert Knight, MD Celgene Corporation
Celgene
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP