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
Results First Received: February 13, 2015  
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
Condition: Multiple Myeloma
Interventions: Drug: Lenalidomide
Drug: Dexamethasone
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 55 sites in Australia, Europe, and Israel. Eligible participants were randomized in a 1:1 ratio to: lenalidomide plus oral pulse high-dose dexamethasone or Placebo plus oral pulse high-dose dexamethasone.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A pre-specified interim analysis revealed a highly significant benefit favoring the lenalidomide/dexamethasone regimen, crossing the pre-specified O'Brien-Fleming superiority boundary. A decision was made to unblind the study allowing those receiving Placebo/dexamethasone to receive the lenalidomide/dexamethasone regimen.

Reporting Groups
  Description
Lenalidomide Plus Dexamethasone (Len/Dex)

Lenalidomide 25 mg by mouth (PO) daily (QD) on Days 1 to 21 and a matching placebo capsule QD on Days 22 to 28 of each 28-day cycle.

Pulse dexamethasone 40mg PO QD on Days 1-4, 9-12, and 17-20 of each 28-day cycle for cycles 1 through 4. Beginning with Cycle 5, dexamethasone dosing schedule was reduced to 40mg PO QD on Days 1 to 4 every 28 days for the remaining cycles.

Placebo Plus Dexamethasone

Placebo PO daily on Days 1 to 28 of each 28 day cycle.

Pulse dexamethasone 40mg PO QD on Days 1-4, 9-12, and 17-20 of each 28-day cycle for Cycles 1 through 4. Beginning with Cycle 5, dexamethasone dosing schedule was reduced to 40mg PO QD for Days 1-4 every 28 days.

Participants with documented progressive disease were permitted to crossover to receive lenalidomide at the same doses mentioned.

After the study was unblinded in August 2005 participants were given the option to add lenalidomide to their dexamethasone treatment regimen immediately or to add lenalidomide to their dexamethasone therapy at the time of disease progression.


Participant Flow for 3 periods

Period 1:   Blinded Treatment (Up to 03 Aug 2005)
    Lenalidomide Plus Dexamethasone (Len/Dex)     Placebo Plus Dexamethasone  
STARTED     176     175  
Safety Population     176 [1]   175 [1]
Evaluable Population     175 [2]   171 [3]
COMPLETED     54 [4]   19 [5]
NOT COMPLETED     122     156  
Adverse Event                 18                 12  
Progression of disease                 67                 122  
Lack of therapeutic effect                 1                 3  
Withdrawal by Subject                 23                 8  
Death                 11                 10  
Unspecified                 2                 1  
[1] Includes those who took at least one dose of study medication regimen
[2] 1 participant excluded because they had no baseline M-protein assessment
[3] 4 participants excluded because they had no baseline M-protein assessment
[4] 54 participants ongoing and continuing on lenalidomide/dexamethasone treatment
[5] Ongoing and includes 15 participants who crossed over to lenalidomide/dexamethasone after unblinding

Period 2:   On Study at Time of Unblinding
    Lenalidomide Plus Dexamethasone (Len/Dex)     Placebo Plus Dexamethasone  
STARTED     176 [1]   175  
COMPLETED     21 [2]   8 [3]
NOT COMPLETED     155     167  
Adverse Event                 22                 12  
Progression of disease                 92                 128  
Lack of Efficacy                 1                 3  
Withdrawal by Subject                 24                 9  
Death                 11                 11  
Unspecified                 5                 4  
[1] Refers to original treatment group assignment in the study.
[2] Participants completed = those continuing on long term Lenalidomide and dexamethasone
[3] Participants completed = those continuing on long term dexamethasone

Period 3:   Long Term Extension (Up to 25 Jun 2013)
    Lenalidomide Plus Dexamethasone (Len/Dex)     Placebo Plus Dexamethasone  
STARTED     21     8 [1]
COMPLETED     0     0  
NOT COMPLETED     21     8  
Adverse Event                 1                 0  
Death                 0                 1  
Unspecified                 12                 4  
Progression of Disease                 7                 3  
Withdrawal by Subject                 1                 0  
[1] 2 participants opted to receive dex alone, 3 crossed over to Len/Dex and 3 added Len at a later date



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat population included all participants who were randomized

Reporting Groups
  Description
Lenalidomide Plus Dexamethasone

Lenalidomide 25 mg by mouth (PO) daily (QD) on Days 1 to 21 and a matching placebo capsule QD on Days 22 to 28 of each 28-day cycle.

Dexamethasone 40mg PO QD on Days 1-4, 9-12, and 17-20 of each 28 day cycle for cycles 1 through 4. Beginning with Cycle 5, dexamethasone dosing schedule was reduced to 40mg PO QD on Days 1 to 4 every 28 days for the remaining cycles.

Placebo Plus Dexamethasone

Placebo PO daily on Days 1 to 28 of each 28 day cycle.

Dexamethasone 40mg PO QD on Days 1-4, 9-12, and 17-20 of each 28-day cycle for Cycles 1 through 4. Beginning with Cycle 5, dexamethasone dosing schedule was reduced to 40mg PO QD for Days 1-4 every 28 days.

Total Total of all reporting groups

Baseline Measures
    Lenalidomide Plus Dexamethasone     Placebo Plus Dexamethasone     Total  
Number of Participants  
[units: participants]
  176     175     351  
Age  
[units: years]
Mean (Standard Deviation)
  62.2  (10.12)     62.9  (8.80)     62.6  (9.47)  
Gender  
[units: participants]
     
Female     72     72     144  
Male     104     103     207  
Eastern Cooperative Oncology Group Performance Status [1]
[units: participants]
     
0 = (Fully Active)     78     65     143  
1 = (Restrictive but Ambulatory)     72     79     151  
2 = Ambulatory unable to Work)     23     27     50  
3 = (Limited Self-Care)     0     1     1  
4 = (Completely Disabled)     0     0     0  
Missing     3     3     6  
Number of Prior Anti-Myeloma Therapies  
[units: participants]
     
1 Prior anti-myeloma therapy     56     57     113  
2 or more prior anti-myeloma therapies     120     118     238  
Time from First Pathological Diagnosis  
[units: years]
Median (Full Range)
  3.4  
  (0.4 to 15.7)  
  4.0  
  (0.3 to 26.6)  
  3.7  
  (0.3 to 26.6)  
Baseline multiple myeloma stage [2]
[units: participants]
     
Stage I     11     8     19  
Stage II     50     57     107  
Stage III     115     110     225  
[1] Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants' disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis.
[2]

The International Staging System divides myeloma into 3 stages based only on the serum beta-2 microglobulin and serum albumin levels.

Stage I: Serum beta-2 microglobulin is less than 3.5 (mg/L) and the albumin level is above 3.5 (g/L);

Stage II: Neither stage I or III, meaning that either:

  • The beta-2 microglobulin level is between 3.5 and 5.5 (with any albumin level), OR
  • The albumin is below 3.5 while the beta-2 microglobulin is less than 3.5

Stage III: Serum beta-2 microglobulin is greater than 5.5.




  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Secondary:   Kaplan-Meier Estimate of Overall Survival (OS)   [ Time Frame: Randomization to data cut off of 03 August 2005; up to 24 months ]

4.  Secondary:   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 ]

5.  Secondary:   Summary of Myeloma Response Rates Based on Best Response Assessment   [ Time Frame: Randomization to 03 August 2005; up to 24 months ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Post-Hoc:   Kaplan-Meier Estimate of Duration of Response   [ Time Frame: Up to data cut off of 03 August 2005; up to 24 months ]

12.  Post-Hoc:   Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008)   [ Time Frame: Up to data cut off of 03 Mar 2008; up to 51 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain, Senior Manager
Organization: Celgene Corporation
phone: 1-866-260-1599
e-mail: ClinicalTrialDisclosure@celgene.com


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Celgene ( 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