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Trial record 95 of 372 for:    LENALIDOMIDE AND Dexamethasone

A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01217957
Recruitment Status : Completed
First Posted : October 8, 2010
Results First Posted : January 27, 2016
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Ixazomib
Drug: Lenalidomide
Drug: Dexamethasone
Enrollment 65
Recruitment Details Participants were enrolled in the study at 10 investigative sites in the United States from 22 November 2010 to data cut-off 08 March 2013.
Pre-assignment Details Participants with a diagnosis of multiple myeloma were enrolled in 1 of 4 dose-escalation cohorts ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2 in combination with lenalidomide, and dexamethasone to establish maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) in Phase 2. 65 participants were enrolled; 15 in phase 1 and 50 in phase 2.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone
Hide Arm/Group Description In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Period Title: Phase 1
Started 3 3 6 3 0
Completed 2 3 5 2 0
Not Completed 1 0 1 1 0
Reason Not Completed
Withdrawal by Patient             1             0             1             1             0
Period Title: Phase 2
Started 0 0 0 0 50
Completed 0 0 0 0 49 [1]
Not Completed 0 0 0 0 1
Reason Not Completed
Withdrawal by Patient             0             0             0             0             1
[1]
Completed=Participants who are ongoing or who have died on study.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1 :Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Total
Hide Arm/Group Description In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 3 3 6 3 50 65
Hide Baseline Analysis Population Description
Safety Analysis Population: all participants who received at least one dose of any of the 3 study drugs.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
62.7  (3.21) 72.3  (4.51) 63.2  (12.19) 64.7  (9.29) 64.2  (11.16) 64.4  (10.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
Female
1
  33.3%
3
 100.0%
3
  50.0%
2
  66.7%
20
  40.0%
29
  44.6%
Male
2
  66.7%
0
   0.0%
3
  50.0%
1
  33.3%
30
  60.0%
36
  55.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
Hispanic or Latino 0 0 0 0 1 1
Not Hispanic or Latino 3 3 6 3 49 64
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
White 3 1 6 0 42 52
Black or African American 0 2 0 3 7 12
Asian 0 0 0 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
3 3 6 3 50 65
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
3 3 6 3 50 65
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
168.9  (12.90) 155.4  (3.20) 165.9  (10.21) 171.1  (8.07) 169.4  (11.57) 168.5  (11.30)
[1]
Measure Description: Height data was available for 3, 3, 6, 3, 48 and 51 participants in each treatment arm, respectively.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
87.43  (12.683) 64.93  (16.045) 72.82  (14.557) 116.63  (25.480) 86.13  (17.695) 85.39  (19.247)
Body Surface Area   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 3 participants 3 participants 6 participants 3 participants 50 participants 65 participants
2.024  (0.2180) 1.665  (0.1923) 1.826  (0.2272) 2.348  (0.3050) 2.011  (0.2343) 1.994  (0.2565)
[1]
Measure Description: Body surface area is defined as [Height(cm) x Weight (kg)]/3600)^1/2. Body surface area data was available for 3, 3, 6, 3, 48 and 51 participants in each treatment arm, respectively.
1.Primary Outcome
Title Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Time Frame Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all patients who received at least one dose of any of the 3 study drugs.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle. for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 3 3 6 3
Measure Type: Number
Unit of Measure: participants
Any AE 3 3 6 3
SAE 2 3 1 2
2.Primary Outcome
Title Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone
Hide Description ORR was defined as the percentage of participants with Complete (CR) + Very Good Partial Response (VGPR) assessed by the investigatory using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or; 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
Time Frame Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the response-evaluable population, defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment, with available data.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23. mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 49 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
59
(44 to 73)
62
(47 to 75)
3.Primary Outcome
Title Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone
Hide Description RP2D will be determined based on number and type of adverse event and serious adverse events, assessments of clinical laboratory values, neurotoxicity grading, and treatment discontinuation.
Time Frame Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All Phase 1 participants.
Arm/Group Title Phase 1: Ixazomib + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: mg/m^2
2.23
4.Primary Outcome
Title Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone
Hide Description MTD of ixazomib will be determined by assessing adverse events and serious adverse events, clinical laboratory values, neurotoxicity grading, and vital sign measurements.
Time Frame Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All Phase 1 participants.
Arm/Group Title Phase 1: Ixazomib + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: mg/m^2
2.97
5.Primary Outcome
Title Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Time Frame Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all patients who received at least one dose of any of the 3 study drugs.
Arm/Group Title Phase 2 :Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 50 53
Measure Type: Number
Unit of Measure: percentage of participants
Grade 3 or Higher AEs 76 75
SAEs 40 43
AEs Resulting in Treatment Discontinuation 8 8
6.Secondary Outcome
Title Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Hide Description Cmax: Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of ixazomib obtained directly from the plasma concentration-time curve.
Time Frame Cycle 1, Days 1 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with available data.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 2 3 4 2
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 (n=1, 3, 4, 1) NA [1]   (NA) 22.303  (13.0184) 94.779  (34.5442) NA [1]   (NA)
Day 15 (n=2, 3, 4, 1) 11.999 [2]   (NA) 31.368  (31.9963) 53.517  (22.1412) NA [1]   (NA)
[1]
Not calculated for 1 participant.
[2]
Not calculated for 2 participants.
7.Secondary Outcome
Title Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
Hide Description Tmax: Time to reach the first maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax, obtained directly from the plasma concentration-time curve.
Time Frame Cycle 1, Days 1 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with data available.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 2 3 4 1
Median (Full Range)
Unit of Measure: hours
Day 1 (n=1, 3, 4, 1)
1.020 [1] 
(NA to NA)
1.520
(1.00 to 8.00)
1.060
(0.50 to 1.08)
0.250 [1] 
(NA to NA)
Day 15 (n=2, 3, 4, 1)
4.165
(1.05 to 7.28)
1.000
(0.98 to 2.03)
1.015
(1.00 to 2.02)
2.000 [1] 
(NA to NA)
[1]
Not calculated for 1 participant.
8.Secondary Outcome
Title Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
Hide Description AUC(0-168) is a measure of the area under the plasma concentration-time curve from time 0 to 168 hours postdose for Ixazomib.
Time Frame Cycle 1, Days 1 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with available data.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 2 3 4 1
Geometric Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
Day 1 (n=1, 3, 4, 1) NA [1]   (NA) 587.667  (350.1861) 923.484  (156.2679) NA [1]   (NA)
Day 15 (n=2, 3, 3, 1) 834.608 [2]   (NA) 1083.998  (104.0256) 1831.324  (262.7420) NA [1]   (NA)
[1]
Not calculated for 1 participant.
[2]
Not calculated for 2 participants.
9.Secondary Outcome
Title Phase 1: Rac: Accumulation Ratio of Ixazomib
Hide Description The accumulation ratio (Rac) was estimated as the ratio of AUC(0-168) on Day 15 to the AUC(0-168) on Day 1. AUC(0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose for ixazomib.
Time Frame Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with available data.
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 1 3 3 0
Geometric Mean (Standard Deviation)
Unit of Measure: Ratio
NA [1]   (NA) 1.849  (0.8359) 2.051  (0.6469)
[1]
Not calculated for 1 participant
10.Secondary Outcome
Title Phase 1: Emax: Maximum Observed Inhibition of Whole Blood 20S Proteasome
Hide Description Emax is the maximum observed inhibition of whole blood 20S proteasome. The pharmacodynamics 20S Proteasome samples were collected and the assays were performed; however, concerns about the third-party laboratory’s performance of the blood 20S proteasome activity assay were identified that precluded the ability to confirm the accuracy of the data so no data is reported.
Time Frame Day 1 predose and at multiple time points (up to 168 hours) postdose and Day 15 predose and at multiple time points (up to 336 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Phase 1: TEmax: Time to the Maximum Observed Inhibition of Whole Blood 20S Proteasome
Hide Description TEmax is the time to the maximum observed inhibition of whole blood 20S proteasome. The pharmacodynamics 20S Proteasome samples were collected and the assays were performed; however, concerns about the third-party laboratory’s performance of the blood 20S proteasome activity assay were identified that precluded the ability to confirm the accuracy of the data so no data is reported.
Time Frame Day 1 predose and at multiple time points (up to 168 hours) postdose and Day 15 predose and at multiple time points (up to 336 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Phase 2: Time to Progression (TTP)
Hide Description TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD).
Time Frame From the first dose of study treatment to the date of first documented progressive disease (Up to 787 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The modified Intent-to-Treat (mITT) population was defined as all patients who received at least one dose of any study drug in phase 2 or who received at least one dose of any study drug and were treated at the phase 2 dose level during phase 1.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 50 53
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimable due to the low number of events.
13.Secondary Outcome
Title Phase 2: Overall Survival (OS)
Hide Description OS was measured as the time in months from the first dose of study treatment to the date of death + 1 day.
Time Frame From the first dose of study treatment to the date of death (up to 787 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included al participants who received 1 of the 3 study drugs. Participants who did not die were censored at the last study visit.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 50 53
Median (95% Confidence Interval)
Unit of Measure: participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimable due to the low number of participants who died.
14.Secondary Outcome
Title Phase 2: Overall Response Rate (ORR)
Hide Description ORR was defined as the percentage of participants with CR, VGPR and Partial Response (PR) assessed by the investigator using IMWG criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
Time Frame Up to 787 days
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population was defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 49 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
88
(75 to 95)
88
(77 to 96)
15.Secondary Outcome
Title Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR)
Hide Description Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
Time Frame After Cycles 3, 6 and 9 (Up to 787 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population was defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 49 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
After 3 cycles
35
(22 to 50)
37
(24 to 51)
After 6 cycles
47
(33 to 62)
48
(34 to 62)
After 9 cycles
57
(42 to 71)
58
(43 to 71)
16.Secondary Outcome
Title Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR)
Hide Description Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. sCR= CR + Normal free light chain (FLC) ratio and Absence of clonal cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. nCR=Positive immunofixation analysis of serum or urine as the only evidence of disease. Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. MR=25% to 49% reduction in serum paraprotein and 50% to 89% reduction in urine light chain excretion for 6 weeks.
Time Frame Cycles 3, 6, 9 and 12 (Up to 787 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population was defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 49 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CR
20
(10 to 34)
23
(13 to 37)
sCR
6
(1 to 17)
10
(3 to 21)
VGPR
39
(25 to 54)
38
(25 to 53)
nCR
2 [1] 
(NA to 11)
2 [1] 
(NA to 10)
PR
67
(52 to 80)
65
(51 to 78)
MR
6
(1 to 17)
6
(1 to 16)
[1]
95% CI lower limit is <1.
17.Secondary Outcome
Title Phase 2: Time to Best Response
Hide Description Time to Best Response was measured as the time in months from the first dose of study treatment to the date of first documented documentation of a confirmed response of partial response (PR) or better.
Time Frame Up to 787 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants form the response-evaluable population, defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment, with available data.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 43 46
Median (Full Range)
Unit of Measure: months
2.96
(0.9 to 11.3)
3.01
(0.9 to 12.9)
18.Secondary Outcome
Title Phase 2: Duration of Response (DOR)
Hide Description DOR was measured as the time in months from the date of first documentation of a confirmed response (CR + PR+ VGPR) to the date of the first documented disease progression (PD). Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
Time Frame Up to 787 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Response Evaluable Population, defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment, with data available for analysis. Patients who did not experience PD were censored at the last response assessment that was SD or better.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 49 52
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimable due to the low number of participants with events (progressive disease).
19.Secondary Outcome
Title Phase 2: Progression Free Survival (PFS)
Hide Description PFS was measured as the time in months from the first dose of study treatment to the date of the first documented PD or death.
Time Frame Up to 787 days
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population was defined as all patients who received at least one dose of any study drug in phase 2 or who received at least one dose of any study drug and were treated at the phase 2 dose level during phase 1.
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 50 53
Median (95% Confidence Interval)
Unit of Measure: months
14.98 [1] 
(13.37 to NA)
NA [1] 
(NA to NA)
[1]
Not estimable due to the low number of participants with events.
20.Secondary Outcome
Title Phase 2: 1 Year Survival Rate
Hide Description 1-year survival rate is defined as the percentage of participants still alive at year after the first dose of stud drug.
Time Frame 1 year after first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone
Hide Arm/Group Description:
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle. for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle. Includes 3 participants who received 2.23 mg/m^2 in Phase 1.
Overall Number of Participants Analyzed 42 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92
(80 to 97)
92
(81 to 97)
Time Frame Up to 787 days
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Phase 1: Ixazomib + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone
Hide Arm/Group Description In phase 1, ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
All-Cause Mortality
Phase 1: Ixazomib + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1: Ixazomib + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   8/15 (53.33%)   20/50 (40.00%) 
Blood and lymphatic system disorders     
Anaemia  1  0/15 (0.00%)  1/50 (2.00%) 
Thrombocytopenia  1  0/15 (0.00%)  1/50 (2.00%) 
Cardiac disorders     
Cardiac failure congestive  1  0/15 (0.00%)  2/50 (4.00%) 
Atrial fibrillation  1  1/15 (6.67%)  0/50 (0.00%) 
Atrial flutter  1  0/15 (0.00%)  1/50 (2.00%) 
Angina pectoris  1  0/15 (0.00%)  1/50 (2.00%) 
Cardio-respiratory arrest  1 [1]  0/15 (0.00%)  1/50 (2.00%) 
Gastrointestinal disorders     
Diarrhoea  1  1/15 (6.67%)  2/50 (4.00%) 
Nausea  1  1/15 (6.67%)  1/50 (2.00%) 
Vomiting  1  1/15 (6.67%)  1/50 (2.00%) 
Constipation  1  0/15 (0.00%)  1/50 (2.00%) 
Gastrooesophageal reflux disease  1  0/15 (0.00%)  1/50 (2.00%) 
Abdominal hernia  1  0/15 (0.00%)  1/50 (2.00%) 
Faecaloma  1  0/15 (0.00%)  1/50 (2.00%) 
Intestinal perforation  1  0/15 (0.00%)  1/50 (2.00%) 
Gastrointestinal haemorrhage  1  1/15 (6.67%)  0/50 (0.00%) 
General disorders     
Asthenia  1  1/15 (6.67%)  1/50 (2.00%) 
Fatigue  1  0/15 (0.00%)  1/50 (2.00%) 
Non-cardiac chest pain  1  0/15 (0.00%)  2/50 (4.00%) 
Pyrexia  1  1/15 (6.67%)  0/50 (0.00%) 
Hernia obstructive  1  0/15 (0.00%)  1/50 (2.00%) 
Oedema peripheral  1  0/15 (0.00%)  1/50 (2.00%) 
Infections and infestations     
Pneumonia  1  1/15 (6.67%)  4/50 (8.00%) 
Diverticulitis  1  0/15 (0.00%)  1/50 (2.00%) 
Bone abscess  1  0/15 (0.00%)  1/50 (2.00%) 
Postoperative wound infection  1  0/15 (0.00%)  1/50 (2.00%) 
Pneumonia respiratory syncytial viral  1 [2]  0/15 (0.00%)  1/50 (2.00%) 
Sepsis  1  0/15 (0.00%)  1/50 (2.00%) 
Injury, poisoning and procedural complications     
Limb traumatic amputation  1  0/15 (0.00%)  1/50 (2.00%) 
Metabolism and nutrition disorders     
Dehydration  1  1/15 (6.67%)  3/50 (6.00%) 
Hypovolaemia  1  1/15 (6.67%)  0/50 (0.00%) 
Hyponatraemia  1  1/15 (6.67%)  0/50 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/15 (0.00%)  3/50 (6.00%) 
Nervous system disorders     
Neuropathy peripheral  1  1/15 (6.67%)  0/50 (0.00%) 
Peripheral sensory neuropathy  1  0/15 (0.00%)  1/50 (2.00%) 
Syncope  1  1/15 (6.67%)  0/50 (0.00%) 
Dizziness  1  1/15 (6.67%)  0/50 (0.00%) 
Psychiatric disorders     
Anxiety  1  0/15 (0.00%)  1/50 (2.00%) 
Renal and urinary disorders     
Renal failure acute  1  0/15 (0.00%)  1/50 (2.00%) 
Renal failure chronic  1  0/15 (0.00%)  1/50 (2.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/15 (0.00%)  1/50 (2.00%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  1/15 (6.67%)  0/50 (0.00%) 
Vascular disorders     
Hypotension  1  1/15 (6.67%)  1/50 (2.00%) 
Orthostatic hypotension  1  1/15 (6.67%)  1/50 (2.00%) 
Deep vein thrombosis  1  1/15 (6.67%)  1/50 (2.00%) 
Embolism  1  0/15 (0.00%)  1/50 (2.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
[1]
One treatment-emergent death occurred in the Phase 2: Ixazomib 4 mg treatment arm and is not related to study treatment.
[2]
One treatment-emergent death occurred in the Phase 2: Ixazomib 4 mg treatment arm and is related to the full regimen (lenalidomide, dexamethasone, and ixazomib).
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1: Ixazomib + Lenalidomide + Dexamethasone Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   15/15 (100.00%)   50/50 (100.00%) 
Blood and lymphatic system disorders     
Leukopenia  1  1/15 (6.67%)  7/50 (14.00%) 
Lymphopenia  1  3/15 (20.00%)  7/50 (14.00%) 
Neutropenia  1  2/15 (13.33%)  16/50 (32.00%) 
Cardiac disorders     
Tachycardia  1  1/15 (6.67%)  5/50 (10.00%) 
Ear and labyrinth disorders     
Deafness  1  1/15 (6.67%)  1/50 (2.00%) 
Tinnitus  1  0/15 (0.00%)  3/50 (6.00%) 
Eye disorders     
Dry eye  1  0/15 (0.00%)  4/50 (8.00%) 
Eye pain  1  1/15 (6.67%)  1/50 (2.00%) 
Vision blurred  1  1/15 (6.67%)  6/50 (12.00%) 
Visual impairment  1  1/15 (6.67%)  1/50 (2.00%) 
Gastrointestinal disorders     
Abdominal discomfort  1  2/15 (13.33%)  1/50 (2.00%) 
Abdominal distension  1  3/15 (20.00%)  5/50 (10.00%) 
Abdominal pain  1  1/15 (6.67%)  4/50 (8.00%) 
Abdominal pain upper  1  1/15 (6.67%)  3/50 (6.00%) 
Dry mouth  1  0/15 (0.00%)  4/50 (8.00%) 
Dyspepsia  1  1/15 (6.67%)  2/50 (4.00%) 
Dysphagia  1  1/15 (6.67%)  2/50 (4.00%) 
Hypoaesthesia oral  1  1/15 (6.67%)  0/50 (0.00%) 
Melaena  1  1/15 (6.67%)  0/50 (0.00%) 
Mouth ulceration  1  1/15 (6.67%)  0/50 (0.00%) 
Oral pain  1  1/15 (6.67%)  0/50 (0.00%) 
Stomatitis  1  1/15 (6.67%)  4/50 (8.00%) 
General disorders     
Chest pain  1  1/15 (6.67%)  0/50 (0.00%) 
Irritability  1  1/15 (6.67%)  2/50 (4.00%) 
Local swelling  1  1/15 (6.67%)  0/50 (0.00%) 
Malaise  1  1/15 (6.67%)  7/50 (14.00%) 
Pain  1  0/15 (0.00%)  4/50 (8.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/15 (6.67%)  0/50 (0.00%) 
Infections and infestations     
Cellulitis  1  2/15 (13.33%)  1/50 (2.00%) 
Folliculitis  1  1/15 (6.67%)  0/50 (0.00%) 
Fungal skin infection  1  1/15 (6.67%)  1/50 (2.00%) 
Herpes simplex  1  1/15 (6.67%)  0/50 (0.00%) 
Nasal vestibulitis  1  1/15 (6.67%)  0/50 (0.00%) 
Nasopharyngitis  1  1/15 (6.67%)  2/50 (4.00%) 
Oral herpes  1  2/15 (13.33%)  2/50 (4.00%) 
Rash pustular  1  1/15 (6.67%)  1/50 (2.00%) 
Skin infection  1  0/15 (0.00%)  3/50 (6.00%) 
Upper respiratory tract infection  1  7/15 (46.67%)  16/50 (32.00%) 
Urinary tract infection  1  0/15 (0.00%)  3/50 (6.00%) 
Injury, poisoning and procedural complications     
Arthropod bite  1  1/15 (6.67%)  0/50 (0.00%) 
Fall  1  1/15 (6.67%)  2/50 (4.00%) 
Sunburn  1  1/15 (6.67%)  0/50 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  0/15 (0.00%)  6/50 (12.00%) 
Aspartate aminotransferase increased  1  0/15 (0.00%)  4/50 (8.00%) 
Blood alkaline phosphatase increased  1  1/15 (6.67%)  4/50 (8.00%) 
Blood creatinine increased  1  1/15 (6.67%)  7/50 (14.00%) 
Blood lactate dehydrogenase increased  1  1/15 (6.67%)  0/50 (0.00%) 
Haemoglobin decreased  1  1/15 (6.67%)  0/50 (0.00%) 
Weight decreased  1  2/15 (13.33%)  3/50 (6.00%) 
Weight increased  1  2/15 (13.33%)  7/50 (14.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/15 (26.67%)  6/50 (12.00%) 
Gout  1  1/15 (6.67%)  1/50 (2.00%) 
Hyperglycaemia  1  0/15 (0.00%)  3/50 (6.00%) 
Hypocalcaemia  1  0/15 (0.00%)  9/50 (18.00%) 
Hypokalaemia  1  4/15 (26.67%)  9/50 (18.00%) 
Hypomagnesaemia  1  1/15 (6.67%)  2/50 (4.00%) 
Hypophosphataemia  1  0/15 (0.00%)  6/50 (12.00%) 
Tumour lysis syndrome  1  1/15 (6.67%)  0/50 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/15 (33.33%)  8/50 (16.00%) 
Bone pain  1  2/15 (13.33%)  5/50 (10.00%) 
Joint stiffness  1  1/15 (6.67%)  1/50 (2.00%) 
Muscle spasms  1  6/15 (40.00%)  9/50 (18.00%) 
Muscular weakness  1  1/15 (6.67%)  4/50 (8.00%) 
Musculoskeletal chest pain  1  3/15 (20.00%)  4/50 (8.00%) 
Musculoskeletal discomfort  1  0/15 (0.00%)  3/50 (6.00%) 
Musculoskeletal pain  1  2/15 (13.33%)  5/50 (10.00%) 
Myalgia  1  1/15 (6.67%)  5/50 (10.00%) 
Neck pain  1  1/15 (6.67%)  0/50 (0.00%) 
Pain in extremity  1  4/15 (26.67%)  11/50 (22.00%) 
Nervous system disorders     
Amnesia  1  0/15 (0.00%)  3/50 (6.00%) 
Dysgeusia  1  3/15 (20.00%)  11/50 (22.00%) 
Headache  1  3/15 (20.00%)  8/50 (16.00%) 
Hypoaesthesia  1  3/15 (20.00%)  3/50 (6.00%) 
Memory impairment  1  1/15 (6.67%)  1/50 (2.00%) 
Paraesthesia  1  1/15 (6.67%)  5/50 (10.00%) 
Sinus headache  1  1/15 (6.67%)  0/50 (0.00%) 
Tremor  1  0/15 (0.00%)  5/50 (10.00%) 
Psychiatric disorders     
Agitation  1  1/15 (6.67%)  1/50 (2.00%) 
Confusional state  1  1/15 (6.67%)  0/50 (0.00%) 
Depression  1  1/15 (6.67%)  3/50 (6.00%) 
Insomnia  1  3/15 (20.00%)  18/50 (36.00%) 
Mental status changes  1  1/15 (6.67%)  1/50 (2.00%) 
Mood swings  1  1/15 (6.67%)  0/50 (0.00%) 
Renal and urinary disorders     
Lower urinary tract symptoms  1  1/15 (6.67%)  0/50 (0.00%) 
Nocturia  1  1/15 (6.67%)  1/50 (2.00%) 
Pollakiuria  1  1/15 (6.67%)  2/50 (4.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/15 (6.67%)  0/50 (0.00%) 
Breast tenderness  1  1/15 (6.67%)  0/50 (0.00%) 
Erectile dysfunction  1  1/15 (6.67%)  1/50 (2.00%) 
Postmenopausal haemorrhage  1  1/15 (6.67%)  0/50 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/15 (26.67%)  14/50 (28.00%) 
Dyspnoea exertional  1  2/15 (13.33%)  1/50 (2.00%) 
Epistaxis  1  0/15 (0.00%)  5/50 (10.00%) 
Nasal congestion  1  2/15 (13.33%)  2/50 (4.00%) 
Oropharyngeal pain  1  2/15 (13.33%)  4/50 (8.00%) 
Pleural effusion  1  1/15 (6.67%)  0/50 (0.00%) 
Productive cough  1  1/15 (6.67%)  0/50 (0.00%) 
Rhinitis allergic  1  1/15 (6.67%)  0/50 (0.00%) 
Rhinorrhoea  1  1/15 (6.67%)  2/50 (4.00%) 
Sinus congestion  1  0/15 (0.00%)  6/50 (12.00%) 
Wheezing  1  1/15 (6.67%)  0/50 (0.00%) 
Skin and subcutaneous tissue disorders     
Acne  1  1/15 (6.67%)  0/50 (0.00%) 
Alopecia  1  1/15 (6.67%)  0/50 (0.00%) 
Angioedema  1  1/15 (6.67%)  0/50 (0.00%) 
Dry skin  1  0/15 (0.00%)  4/50 (8.00%) 
Erythema  1  1/15 (6.67%)  3/50 (6.00%) 
Macule  1  1/15 (6.67%)  0/50 (0.00%) 
Night sweats  1  1/15 (6.67%)  3/50 (6.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/15 (6.67%)  0/50 (0.00%) 
Pruritus  1  1/15 (6.67%)  3/50 (6.00%) 
Rash  1  0/15 (0.00%)  4/50 (8.00%) 
Rash erythematous  1  3/15 (20.00%)  4/50 (8.00%) 
Rash macular  1  0/15 (0.00%)  10/50 (20.00%) 
Rash papular  1  2/15 (13.33%)  1/50 (2.00%) 
Rash pruritic  1  2/15 (13.33%)  6/50 (12.00%) 
Skin exfoliation  1  2/15 (13.33%)  0/50 (0.00%) 
Skin hyperpigmentation  1  0/15 (0.00%)  3/50 (6.00%) 
Skin lesion  1  1/15 (6.67%)  1/50 (2.00%) 
Skin ulcer  1  1/15 (6.67%)  0/50 (0.00%) 
Urticaria  1  1/15 (6.67%)  1/50 (2.00%) 
Vascular disorders     
Hypertension  1  4/15 (26.67%)  1/50 (2.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director, Clinical Science
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01217957     History of Changes
Other Study ID Numbers: C16005
U1111-1176-7340 ( Registry Identifier: WHO )
First Submitted: September 24, 2010
First Posted: October 8, 2010
Results First Submitted: December 4, 2015
Results First Posted: January 27, 2016
Last Update Posted: March 14, 2018