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A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT01564537
First received: March 22, 2012
Last updated: January 16, 2017
Last verified: January 2017
Results First Received: December 19, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Interventions: Drug: Ixazomib
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
Participants enrolled in this study at 147 sites in Australia, Austria, Belgium, Canada, China, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Republic of Korea, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Singapore, Spain, Sweden, Turkey, United Kingdom and US from 28 Aug 2012 to 27 May 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of relapsed and/or refractory multiple myeloma were enrolled in 1 of 2 treatment groups: Ixazomib 4 mg or Ixazomib placebo-matching tablets in combination with lenalidomide, and dexamethasone. Data cut-off for this first analysis was 30 October 2014. The study is continuing in a double-blind fashion.

Reporting Groups
  Description
Ixazomib+ Lenalidomide + Dexamethasone Ixazomib 4 mg, capsules, orally, once, on Days 1, 8 and 15; plus lenalidomide 25 mg, orally, once, on Days 1 through 21; and dexamethasone 40 mg, orally, once, on Days 1, 8, 15 and 22 of a 28-day cycle for multiple cycles until progressive disease (PD) or unacceptable toxicity, whichever occurred first up to end of treatment (EOT) projected at 80 months.
Placebo + Lenalidomide + Dexamethasone Ixazomib placebo-matching capsules, orally, once, on Days 1, 8 and 15; plus lenalidomide 25 mg, orally, once, on Days 1 through 21; and dexamethasone 40 mg, orally, once, on Days 1, 8, 15 and 22 of a 28-day cycle for multiple cycles until progressive disease (PD) or unacceptable toxicity, whichever occurred first up to EOT projected at 80 months.

Participant Flow:   Overall Study
    Ixazomib+ Lenalidomide + Dexamethasone   Placebo + Lenalidomide + Dexamethasone
STARTED   360   362 
Safety Population: Received Study Drug   360   360 
COMPLETED   354 [1]   356 [1] 
NOT COMPLETED   6   6 
Withdrawal by Participant                4                4 
Lost to Follow-up                1                0 
Other Miscellaneous Reasons                1                2 
[1] Completed=Participants who are ongoing as of 30 October 2014 or who have died on study.



  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 (ITT) population was defined as all randomized participants.

Reporting Groups
  Description
Ixazomib+ Lenalidomide + Dexamethasone Ixazomib 4 mg, capsules, orally, once, on Days 1, 8 and 15; plus lenalidomide 25 mg, orally, once, on Days 1 through 21; and dexamethasone 40 mg, orally, once, on Days 1, 8, 15 and 22 of a 28-day cycle for multiple cycles until progressive disease (PD) or unacceptable toxicity, whichever occurred first up to EOT projected at 80 months.
Placebo + Lenalidomide + Dexamethasone Ixazomib placebo-matching capsules, orally, once, on Days 1, 8 and 15; plus lenalidomide 25 mg, orally, once, on Days 1 through 21; and dexamethasone 40 mg, orally, once, on Days 1, 8, 15 and 22 of a 28-day cycle for multiple cycles until progressive disease (PD) or unacceptable toxicity, whichever occurred first up to EOT projected at 80 months.
Total Total of all reporting groups

Baseline Measures
   Ixazomib+ Lenalidomide + Dexamethasone   Placebo + Lenalidomide + Dexamethasone   Total 
Overall Participants Analyzed 
[Units: Participants]
 360   362   722 
Age 
[Units: Years]
Mean (Standard Deviation)
 65.5  (9.13)   65.8  (9.70)   65.7  (9.41) 
Age, Customized 
[Units: Participants]
     
≤65 years   168   176   344 
>65-≤75 years   145   125   270 
>75 years   47   61   108 
Gender 
[Units: Participants]
Count of Participants
     
Female      153  42.5%      160  44.2%      313  43.4% 
Male      207  57.5%      202  55.8%      409  56.6% 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   310   301   611 
Black or African American   7   6   13 
Native Hawaiian/Other Pacific Islander   2   2   4 
Asian   30   34   64 
American Indian/Alaska native   0   1   1 
Other   4   3   7 
Not reported   7   15   22 
Race/Ethnicity, Customized 
[Units: Participants]
     
Hispanic or Latino   9   12   21 
Not Hispanic or Latino   339   333   672 
Not Reported   10   15   25 
Missing   2   2   4 
Region of Enrollment 
[Units: Participants]
     
Russian Federation   21   18   39 
Singapore   2   4   6 
United States   28   23   51 
Portugal   7   8   15 
Austria   5   4   9 
Netherlands   3   6   9 
Sweden   15   12   27 
China   3   3   6 
Korea, Republic of   4   2   6 
Poland   21   20   41 
France   36   45   81 
Romania   6   6   12 
Hungary   18   21   39 
United Kingdom   12   8   20 
Spain   16   14   30 
New Zealand   28   39   67 
Canada   19   26   45 
Czech Republic   15   21   36 
Turkey   4   3   7 
Belgium   7   7   14 
Denmark   10   7   17 
Italy   24   15   39 
Israel   19   14   33 
Australia   9   8   17 
Germany   8   7   15 
Japan   20   21   41 
Stratification Factor: Lines of Prior Therapy 
[Units: Participants]
     
1 Line   212   213   425 
2 or 3 Lines   148   149   297 
Stratification Factor: Proteasome Inhibitor 
[Units: Participants]
     
Exposed   250   253   503 
Naïve   110   109   219 
Stratification Factor: International Staging System (ISS) Stag at Screening [1] 
[Units: Participants]
     
Stage I or Stage II   314   318   632 
Stage III   46   44   90 
[1] Stage I: Serum beta2-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL; Stage II: Neither Stage I or III, meaning that either: beta2-microglobulin level ≥3.5 and <5.5 mg/L (with any albumin level), OR albumin <3.5 g/dL with beta2-microglobulin <3.5 mg/L; Stage III: Serum beta2-microglobulin ≥5.5 mg/L. Normal serum beta2-microglobulin: <3.0 mg/L; normal albumin: 3.5–5.0 g/dL.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)   [ Time Frame: From date of randomization until disease progression or death up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: Date of randomization until death up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

3.  Secondary:   Overall Response Rate (ORR) as Assessed by the IRC   [ Time Frame: Day 1 of each cycle (every 4 weeks) until disease progression up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

4.  Secondary:   Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) as Assessed by the IRC   [ Time Frame: Day 1 of each cycle (every 4 weeks) until disease progression up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

5.  Secondary:   Duration of Response (DOR)   [ Time Frame: Day 1 of each cycle (every 4 weeks) until disease progression up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

6.  Secondary:   Time to Progression (TTP) as Assessed by the IRC   [ Time Frame: Day 1 of each cycle (every 4 weeks) until disease progression up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

7.  Secondary:   Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: From the date of signing of the informed consent form through 30 days after the last dose of study drug up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

8.  Secondary:   PFS in High-Risk Participants   [ Time Frame: From date of randomization until disease progression or death up to data cut-off: 30 October 2014 (approximate median follow-up 15 months) ]

9.  Secondary:   Overall Survival in High-Risk Participants Carrying Deletion 17 [Del(17)]   [ Time Frame: At the time of screening; Day 1 of each cycle (every 4 weeks) until disease progression and thereafter every 12 weeks until death or study termination ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  

10.  Secondary:   Percentage of Participants Achieving Pain Response   [ Time Frame: At screening; Day 1 of each cycle; and thereafter every 4 weeks until disease progression ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  

11.  Secondary:   Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)   [ Time Frame: Baseline and Every 2 Cycles beginning with Cycle 2 during treatment period, End of Treatment (EOT), and every 4 Weeks in follow-up ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  

12.  Secondary:   Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)   [ Time Frame: Baseline and Every 2 Cycles beginning with Cycle 2 during treatment period, End of Treatment (EOT), and every 4 Weeks in follow-up ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  

13.  Secondary:   OS in High-Risk Participants   [ Time Frame: At the time of screening; Day 1 of each cycle; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  

14.  Secondary:   Pharmacokinetic Parameters (Including Cmax, AUC and Tmax) of Ixazomib   [ Time Frame: Days 1 & 14 of Cycles 1 & 2. Day 1 of Cycles 3 to 10 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  

15.  Secondary:   Association Between Response or Resistance to Ixazomib Treatment and Proteasome and Nuclear Factor–kB (NF-kB)-Related Genes   [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination ]
Results not yet reported.   Anticipated Reporting Date:   12/2020  


  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: Medical Director, Clinical Science
Organization: Takeda
phone: +1-877-825-3327
e-mail: trialdisclosures@takeda.com


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

Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01564537     History of Changes
Other Study ID Numbers: C16010
2011-005496-17 ( EudraCT Number )
CTR20130908 ( Registry Identifier: SFDA CTR )
U1111-1164-7646 ( Registry Identifier: WHO )
NL40132.018.12 ( Registry Identifier: CCMO )
12/LO/0949 ( Registry Identifier: NRES )
JapicCTI-132345 ( Registry Identifier: JapicCTI )
1015042370 ( Registry Identifier: TCTIN )
C16010CTIL ( Registry Identifier: Israel )
Study First Received: March 22, 2012
Results First Received: December 19, 2015
Last Updated: January 16, 2017