Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Study of Oral IXAZOMIB in Combination With Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01383928
First received: June 27, 2011
Last updated: May 3, 2016
Last verified: November 2015
Results First Received: November 16, 2015  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Intervention: Drug: IXAZOMIB + Lenalidomide + Dexamethasone

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 15 investigative sites in the United States from 31 October 2011 to 06 April 2015.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with newly diagnosed multiple myeloma were enrolled in 1 of the 3 treatment arms: ixazomib 3 milligram (mg) and 3.7 mg during Phase 1 and ixazomib 3 mg during Phase 2.

Reporting Groups
  Description
Phase 1: Ixazomib 3 mg Ixazomib (MLN9708) 3 mg, capsules, orally, twice-weekly on Days 1, 4, 8, and 11, lenalidomide 25 mg, capsules, orally, once daily on Days 1-14, dexamethasone 20 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 1-8 and dexamethasone 10 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 9-16 in 21-day treatment cycles for up to 16 cycles in the absence of disease progression or unacceptable toxicity as induction therapy during Phase 1. Participants with stable or responding disease continued receiving ixazomib (MLN9708) 3 mg, capsules, orally, twice weekly on Days 1, 4, 8, and 11 in 21-day treatment cycles as maintenance therapy until progressive disease or unacceptable toxicity.
Phase 1: Ixazomib 3.7 mg Ixazomib (MLN9708) 3.7 mg, capsules, orally, twice-weekly on Days 1, 4, 8, and 11, lenalidomide 25 mg, capsules, orally, once daily on Days 1-14, dexamethasone 20 mg, capsules, orally, once daily on days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 1-8 and dexamethasone 10 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 9-16 in 21-day treatment cycles for up to 16 cycles in the absence of disease progression or unacceptable toxicity as induction therapy during Phase 1. Participants with stable or responding disease continued receiving ixazomib (MLN9708) 3.7 mg, capsules, orally, twice weekly on Days 1, 4, 8, and 11 in 21-day treatment cycles as maintenance therapy until progressive disease or unacceptable toxicity.
Phase 2: Ixazomib 3 mg Ixazomib 3 mg (MLN9708), capsules, orally, twice-weekly on Days 1, 4, 8, and 11, lenalidomide 25 mg capsules, orally, once daily on Days 1-14, dexamethasone 20 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11 and 12 in Cycle 1-8 and dexamethasone 10 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11 and 12 in Cycle 9-16 in 21-day treatment cycles for up to 16 cycles in the absence of disease progression or unacceptable toxicity as induction therapy during Phase 2. Participants with stable or responding disease continued receiving ixazomib (MLN9708) 3 mg, capsules, orally, twice weekly on Days 1, 4, 8, and 11 in 21-day treatment cycles as maintenance therapy until progressive disease or unacceptable toxicity.

Participant Flow for 2 periods

Period 1:   Phase 1
    Phase 1: Ixazomib 3 mg   Phase 1: Ixazomib 3.7 mg   Phase 2: Ixazomib 3 mg
STARTED   7   7   0 
COMPLETED   2   0   0 
NOT COMPLETED   5   7   0 
Autologous Stem Cell Transplantation                2                1                0 
Adverse Event                1                2                0 
Other                1                3                0 
Progressive Disease                1                1                0 

Period 2:   Phase 2
    Phase 1: Ixazomib 3 mg   Phase 1: Ixazomib 3.7 mg   Phase 2: Ixazomib 3 mg
STARTED   0   0   50 
COMPLETED   0   0   10 
NOT COMPLETED   0   0   40 
Autologous Stem Cell Transplantation                0                0                18 
Adverse Event                0                0                8 
Other                0                0                4 
Progressive Disease                0                0                5 
Withdrawal by Subject                0                0                4 
Unsatisfactory therapeutic response                0                0                1 



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Safety population included all participants who received at least 1 dose of any study drug.

Reporting Groups
  Description
Phase 1: Ixazomib 3 mg Ixazomib (MLN9708) 3 mg, capsules, orally, twice-weekly on Days 1, 4, 8, and 11, lenalidomide 25 mg, capsules, orally, once daily on Days 1-14, dexamethasone 20 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 1-8 and dexamethasone 10 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 9-16 in 21-day treatment cycles for up to 16 cycles in the absence of disease progression or unacceptable toxicity as induction therapy during Phase 1. Participants with stable or responding disease continued receiving ixazomib (MLN9708) 3 mg, capsules, orally, twice weekly on Days 1, 4, 8, and 11 in 21-day treatment cycles as maintenance therapy until progressive disease or unacceptable toxicity.
Phase 1: Ixazomib 3.7 mg Ixazomib (MLN9708) 3.7 mg, capsules, orally, twice-weekly on Days 1, 4, 8, and 11, lenalidomide 25 mg, capsules, orally, once daily on Days 1-14, dexamethasone 20 mg, capsules, orally, once daily on days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 1-8 and dexamethasone 10 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycle 9-16 in 21-day treatment cycles for up to 16 cycles in the absence of disease progression or unacceptable toxicity as induction therapy during Phase 1. Participants with stable or responding disease continued receiving ixazomib (MLN9708) 3.7 mg, capsules, orally, twice weekly on Days 1, 4, 8, and 11 in 21-day treatment cycles as maintenance therapy until progressive disease or unacceptable toxicity.
Phase 2: Ixazomib 3 mg Ixazomib 3 mg (MLN9708), capsules, orally, twice-weekly on Days 1, 4, 8, and 11, lenalidomide 25 mg capsules, orally, once daily on Days 1-14, dexamethasone 20 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11 and 12 in Cycle 1-8 and dexamethasone 10 mg, capsules, orally, once daily on Days 1, 2, 4, 5, 8, 9, 11 and 12 in Cycle 9-16 in 21-day treatment cycles for up to 16 cycles in the absence of disease progression or unacceptable toxicity as induction therapy during Phase 2. Participants with stable or responding disease continued receiving ixazomib (MLN9708) 3 mg, capsules, orally, twice weekly on Days 1, 4, 8, and 11 in 21-day treatment cycles as maintenance therapy until progressive disease or unacceptable toxicity.
Total Total of all reporting groups

Baseline Measures
   Phase 1: Ixazomib 3 mg   Phase 1: Ixazomib 3.7 mg   Phase 2: Ixazomib 3 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 7   7   50   64 
Age 
[Units: Years]
Mean (Standard Deviation)
 64.3  (12.04)   61.1  (6.20)   61.5  (10.03)   61.8  (9.82) 
Gender 
[Units: Participants]
       
Female   2   3   19   24 
Male   5   4   31   40 
Race/Ethnicity, Customized 
[Units: Participants]
       
Hispanic or Latino   0   0   1   1 
Not Hispanic or Latino   7   7   48   62 
Not Reported   0   0   1   1 
Race/Ethnicity, Customized 
[Units: Participants]
       
White   5   7   42   54 
Black or African American   1   0   7   8 
Other   1   0   0   1 
Not Reported   0   0   1   1 
Region of Enrollment 
[Units: Participants]
       
United States   7   7   50   64 
Height [1] 
[Units: Centimeter (cm)]
Mean (Standard Deviation)
 171.1  (13.09)   170.9  (7.10)   171.2  (9.30)   171.1  (9.43) 
[1] For this baseline measure, number of participants evaluable were 7, 6 and 49 for each arm, respectively.
Weight 
[Units: Kilogram (kg)]
Mean (Standard Deviation)
 94.29  (17.083)   82.56  (19.295)   81.22  (16.701)   82.80  (17.228) 
Body Surface Area (BSA) [1] 
[Units: Square meter (m^2)]
Mean (Standard Deviation)
 2.109  (0.2192)   1.960  (0.2657)   1.958  (0.2373)   1.975  (0.2390) 
[1] For this baseline measure, number of participants evaluable were 7, 6 and 49 for each arm, respectively.
Type of Myeloma [1] 
[Units: Participants]
       
IgG Kappa   2   3   24   29 
IgG Lambda   1   1   7   9 
IgA Kappa   1   1   10   12 
IgA Lambda   1   0   3   4 
Biclonal   0   1   1   2 
Lambda Free Light Chains   1   0   3   4 
Kappa Free Light Chains   1   1   1   3 
Unknown   0   0   1   1 
[1] Types of Myeloma was described on the basis of antibodies produced by cancerous plasma cells.
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] 
[Units: Participants]
       
 3   5   27   35 
 4   1   21   26 
 0   1   2   3 
[1] ECOG performance status is used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead.
Serum Creatinine 
[Units: Milligram per deciliter (mg/dL)]
Mean (Standard Deviation)
 1.33  (0.435)   1.07  (0.269)   1.04  (0.257)   1.07  (0.291) 
Serum Creatinine Category 
[Units: Participants]
       
Less than or equal to (<=) 2 mg/dL   7   7   50   64 
Greater than (>) 2 mg/dL   0   0   0   0 
Creatinine Clearance [1] 
[Units: Milliliter per minute (mL/min)]
Mean (Standard Deviation)
 81.847  (39.0758)   83.527  (31.9197)   84.128  (27.8796)   83.813  (29.1122) 
[1] Creatinine clearance was calculated using the Cockcroft-Gault formula: C*[140-Age(years)]*Weight (kg)/[72 x serum creatinine (mg/dL)], where multiplication factor C = 1 for males, and C = 0.85 for females.
Creatinine Clearance Category 
[Units: Participants]
       
30 - 60 mL/min   2   2   8   12 
>60 mL/min   5   5   42   52 
Corrected Calcium [1] 
[Units: mg/dL]
Mean (Standard Deviation)
 9.83  (0.275)   9.79  (0.561)   10.01  (0.617)   9.96  (0.583) 
[1] Corrected calcium was calculated using the following formula: serum calcium (mg/dL)+0.98*[4-serum albumin (gram per deciliter [g/dL])]
Hemoglobin 
[Units: Gram per liter (g/L)]
Mean (Standard Deviation)
 103.4  (21.59)   112.0  (16.42)   108.9  (14.36)   108.6  (15.32) 
Skeletal Survey 
[Units: Participants]
       
Performed Skeletal Survey   6   5   46   57 
Did not Performed Skeletal Survey   1   2   4   7 
Participants with skeletal survey results [1] 
[Units: Participants]
       
Within Normal Limits   0   0   3   3 
Abnormal, not clinically significant   2   3   21   26 
Abnormal, clinically significant   4   2   22   28 
[1] Participants who performed skeletal survey were eligible for this baseline measure.
Participants with Lytic Bone Lesions Present 
[Units: Participants]
       
Present   5   3   37   45 
Not Present   1   2   7   10 
Indeterminate   0   0   1   1 
Missing   1   2   5   8 
Participants with Extramedullary Plasmacytomas [1] 
[Units: Participants]
       
Plasmacytomas Present   1   1   18   20 
Plasmacytomas Not Present   2   2   4   8 
Not Reported   4   4   28   36 
[1] Participants who performed magnetic resonance imaging (MRI)/computed tomography (CT) scan were eligible for this baseline measure.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase 1: Maximum Tolerated Dose (MTD)   [ Time Frame: Cycle 1 ]

2.  Primary:   Phase 1: Recommended Phase 2 Dose (RP2D)   [ Time Frame: Cycle 1 up to Cycle 35 ]

3.  Primary:   Phase 1: Percentage of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)   [ Time Frame: Baseline up to 30 days after last dose of study drug ]

4.  Primary:   Phase 1: Number of Participants With Change From Baseline Value in Clinical Laboratory Test Results to Worst Value   [ Time Frame: Baseline and Cycle 1 up to Cycle 35 ]

5.  Primary:   Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAE) Related to Neurotoxicity   [ Time Frame: Baseline up to 30 days after last dose of study drug ]

6.  Primary:   Phase 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs   [ Time Frame: Baseline and Day 1 of each treatment cycle up to 35 treatment cycles ]

7.  Primary:   Phase 2: Percentage of Participants With Complete Response (CR) + Very Good Partial Response (VGPR)   [ Time Frame: Baseline up to treatment cycle 35 ]

8.  Primary:   Phase 2: Percentage of Participants With Grade 3 or Higher Adverse Events   [ Time Frame: Baseline up to 30 days after last dose of study drug ]

9.  Primary:   Phase 2: Percentage of Participants Experiencing Serious Adverse Events   [ Time Frame: Baseline up to 30 days after last dose of study drug ]

10.  Primary:   Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Study Drug Discontinuation   [ Time Frame: Baseline up to 30 days after last dose of study drug ]

11.  Secondary:   Phase 1: Cmax: Maximum Plasma Concentration for Ixazomib   [ Time Frame: Cycle 1, Days 1 and 11 ]

12.  Secondary:   Phase 1: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib   [ Time Frame: Cycle 1, Days 1 and 11 ]

13.  Secondary:   Phase 1: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib   [ Time Frame: Cycle 1, Days 1 and 11 ]

14.  Secondary:   Phase 1: Rac: Accumulation Ratio of Ixazomib   [ Time Frame: Cycle 1, Days 1 and 11 ]

15.  Secondary:   Phase 1: Percentage of Participants With Best Overall Response   [ Time Frame: Baseline until end of study treatment (up to Cycle 35) ]

16.  Secondary:   Phase 2: Percentage of Participants With Objective Response   [ Time Frame: Baseline until end of study treatment (up to Cycle 35) ]

17.  Secondary:   Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After Cycles 4, 8, and 16   [ Time Frame: Cycles 4, 8, and 16 ]

18.  Secondary:   Phase 2: Pecentage of Participants With Complete Response (CR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

19.  Secondary:   Phase 2: Percentage of Participants With Stringent Complete Response (sCR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

20.  Secondary:   Phase 2: Percentage of Participants With Very Good Partial Response (VGPR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

21.  Secondary:   Phase 2: Percentage of Participants With Near Complete Response (nCR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

22.  Secondary:   Phase 2: Percentage of Participants With Partial Response (PR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

23.  Secondary:   Phase 2: Percentage of Participants With Minimal Response (MR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

24.  Secondary:   Phase 2: Time to Response   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

25.  Secondary:   Phase 2: Duration of Response (DOR)   [ Time Frame: Baseline until end of study treatment (up to treatment cycle 35) ]

26.  Secondary:   Phase 2: Time to Disease Progression (TTP)   [ Time Frame: Baseline until progressive disease (up to treatment cycle 35) ]

27.  Secondary:   Phase 2: Progression Free Survival (PFS)   [ Time Frame: Baseline until progressive disease (up to treatment cycle 35) ]

28.  Secondary:   Phase 2: Percentage of Participants Achieving Survival at Year 1   [ Time Frame: 1 year after the first dose of study treatment ]

29.  Secondary:   Phase 2: Overall Survival   [ Time Frame: Baseline up to treatment cycle 35 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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
Organization: Takeda
phone: +1-877-825-3327
e-mail: trialdisclosures@takeda.com



Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01383928     History of Changes
Other Study ID Numbers: C16008
U1111-1168-1172 ( Registry Identifier: WHO (UTN) )
Study First Received: June 27, 2011
Results First Received: November 16, 2015
Last Updated: May 3, 2016
Health Authority: United States: Food and Drug Administration