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Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma (CLARION)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01818752
First Posted: March 26, 2013
Last Update Posted: August 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Amgen
Results First Submitted: July 3, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: Carfilzomib
Drug: Bortezomib
Drug: Melphalan
Drug: Prednisone

  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
This study was conducted at 183 centers in Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Romania, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, and United States.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants were randomized in a 1:1 ratio. Randomization was stratified by International Staging System (ISS) stage (stage 1 versus stages 2 or 3), choice of route of bortezomib administration (intravenous [IV] versus subcutaneous [SC]), region (North America, Europe, Asia Pacific, or other), and age (< 75 years versus ≥ 75 years).

Reporting Groups
  Description
Bortezomib, Melphalan, Prednisone Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Carfilzomib, Melphalan, Prednisone Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Participant Flow:   Overall Study
    Bortezomib, Melphalan, Prednisone   Carfilzomib, Melphalan, Prednisone
STARTED   477   478 
Received Treatment   470   474 
COMPLETED   290 [1]   280 [1] 
NOT COMPLETED   187   198 
Adverse Event                64                74 
Death                14                18 
Non-compliance                16                20 
Withdrawal by Subject                15                14 
Physician Decision                9                8 
Disease Progression                54                48 
Other                7                8 
Continuing Treatment                1                4 
Randomized but not Dosed                7                4 
[1] Completed treatment



  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.
No text entered.

Reporting Groups
  Description
Bortezomib, Melphalan, Prednisone Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Carfilzomib, Melphalan, Prednisone Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Total Total of all reporting groups

Baseline Measures
   Bortezomib, Melphalan, Prednisone   Carfilzomib, Melphalan, Prednisone   Total 
Overall Participants Analyzed 
[Units: Participants]
 477   478   955 
Age 
[Units: Years]
Mean (Standard Deviation)
 71.5  (6.5)   72.0  (5.7)   71.7  (6.1) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      238  49.9%      235  49.2%      473  49.5% 
Male      239  50.1%      243  50.8%      482  50.5% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      15   3.1%      18   3.8%      33   3.5% 
Not Hispanic or Latino      443  92.9%      427  89.3%      870  91.1% 
Unknown or Not Reported      19   4.0%      33   6.9%      52   5.4% 
Race/Ethnicity, Customized 
[Units: Participants]
     
American Indian or Alaska Native   2   1   3 
Asian   121   123   244 
Black or African American   0   3   3 
White   339   329   668 
Other   3   1   4 
Multiple   0   2   2 
Not Reported   12   19   31 
Stratification Factor: International Staging System (ISS) Stage [1] 
[Units: Participants]
     
Stage I   99   95   194 
Stage II or III   378   383   761 
[1]

The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group:

  • Stage I: β2-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL
  • Stage II: β2M < 3.5 mg/L and albumin < 3.5 g/dL; or β2M 3.5 mg/L - 5.5 mg/L irrespective of the serum albumin
  • Stage III: β2M ≥ 5.5 mg/L
Stratification Factor: Route of Bortezomib Administration [1] 
[Units: Participants]
     
Intravenous   123   123   246 
Subcutaneous   354   355   709 
[1] The route of bortezomib administration (IV versus SC) was made per investigator's choice, dose modification, or regulatory approval. The investigator selected the route for all participants prior to randomization to treatment group in order to minimize any evaluation bias because of imbalances in potential prognostic factors that might have impacted the investigator’s choice of a particular route.
Stratification Factor: Region of Enrollment 
[Units: Participants]
     
Asia Pacific   141   140   281 
North America   12   8   20 
Europe   317   320   637 
Other   7   10   17 
Stratification Factor: Age 
[Units: Participants]
     
< 75 years   329   327   656 
≥ 75 years   148   151   299 
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] 
[Units: Participants]
     
0 (Fully active)   125   129   254 
1 (Restrictive but ambulatory)   250   260   510 
2 (Ambulatory but unable to work)   101   89   190 
Missing   1   0   1 
[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. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression-Free Survival (PFS)   [ Time Frame: From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively. ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively. ]

3.  Secondary:   Overall Response Rate   [ Time Frame: Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively. ]

4.  Secondary:   Complete Response Rate   [ Time Frame: Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively. ]

5.  Secondary:   Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy   [ Time Frame: From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups. ]

6.  Secondary:   European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores   [ Time Frame: Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48 ]

7.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups. ]


  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: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


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

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01818752     History of Changes
Other Study ID Numbers: 2012-005
2012-005283-97 ( EudraCT Number )
20130397 ( Other Identifier: Amgen Inc. )
First Submitted: February 12, 2013
First Posted: March 26, 2013
Results First Submitted: July 3, 2017
Results First Posted: August 1, 2017
Last Update Posted: August 30, 2017