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Trial record 1 of 1 for:    NCT01564537
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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):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01564537
First received: March 22, 2012
Last updated: May 3, 2016
Last verified: December 2015
Results First Received: December 19, 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
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  
Number of Participants  
[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]
     
Female     153     160     313  
Male     207     202     409  
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
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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   Safety Issue:   No

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   Safety Issue:   No

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   Safety Issue:   No

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   Safety Issue:   No

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   Safety Issue:   No

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   Safety Issue:   No

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   Safety Issue:   No


  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: 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: May 3, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Ministry of Health
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency