Trial Outcomes & Findings for A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma (NCT NCT01217957)

Last Updated: 2018-03-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)

Results posted on

2018-03-14

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone 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.
Phase 1 STARTED	3	3	6	3	0
Phase 1 COMPLETED	2	3	5	2	0
Phase 1 NOT COMPLETED	1	0	1	1	0
Phase 2 STARTED	0	0	0	0	50
Phase 2 COMPLETED	0	0	0	0	49
Phase 2 NOT COMPLETED	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone 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.
Phase 1 Withdrawal by Patient	1	0	1	1	0
Phase 2 Withdrawal by Patient	0	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1 :Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone n=6 Participants 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone n=50 Participants 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 n=65 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 3.21 • n=93 Participants	72.3 years STANDARD_DEVIATION 4.51 • n=4 Participants	63.2 years STANDARD_DEVIATION 12.19 • n=27 Participants	64.7 years STANDARD_DEVIATION 9.29 • n=483 Participants	64.2 years STANDARD_DEVIATION 11.16 • n=36 Participants	64.4 years STANDARD_DEVIATION 10.67 • n=10 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	20 Participants n=36 Participants	29 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	1 Participants n=483 Participants	30 Participants n=36 Participants	36 Participants n=10 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	1 participants n=10 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 participants n=93 Participants	3 participants n=4 Participants	6 participants n=27 Participants	3 participants n=483 Participants	49 participants n=36 Participants	64 participants n=10 Participants
Race/Ethnicity, Customized White	3 participants n=93 Participants	1 participants n=4 Participants	6 participants n=27 Participants	0 participants n=483 Participants	42 participants n=36 Participants	52 participants n=10 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=93 Participants	2 participants n=4 Participants	0 participants n=27 Participants	3 participants n=483 Participants	7 participants n=36 Participants	12 participants n=10 Participants
Race/Ethnicity, Customized Asian	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	1 participants n=10 Participants
Region of Enrollment United States	3 participants n=93 Participants	3 participants n=4 Participants	6 participants n=27 Participants	3 participants n=483 Participants	50 participants n=36 Participants	65 participants n=10 Participants
Height	168.9 cm STANDARD_DEVIATION 12.90 • n=93 Participants	155.4 cm STANDARD_DEVIATION 3.20 • n=4 Participants	165.9 cm STANDARD_DEVIATION 10.21 • n=27 Participants	171.1 cm STANDARD_DEVIATION 8.07 • n=483 Participants	169.4 cm STANDARD_DEVIATION 11.57 • n=36 Participants	168.5 cm STANDARD_DEVIATION 11.30 • n=10 Participants
Weight	87.43 kg STANDARD_DEVIATION 12.683 • n=93 Participants	64.93 kg STANDARD_DEVIATION 16.045 • n=4 Participants	72.82 kg STANDARD_DEVIATION 14.557 • n=27 Participants	116.63 kg STANDARD_DEVIATION 25.480 • n=483 Participants	86.13 kg STANDARD_DEVIATION 17.695 • n=36 Participants	85.39 kg STANDARD_DEVIATION 19.247 • n=10 Participants
Body Surface Area	2.024 m^2 STANDARD_DEVIATION 0.2180 • n=93 Participants	1.665 m^2 STANDARD_DEVIATION 0.1923 • n=4 Participants	1.826 m^2 STANDARD_DEVIATION 0.2272 • n=27 Participants	2.348 m^2 STANDARD_DEVIATION 0.3050 • n=483 Participants	2.011 m^2 STANDARD_DEVIATION 0.2343 • n=36 Participants	1.994 m^2 STANDARD_DEVIATION 0.2565 • n=10 Participants

PRIMARY outcome

Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)

Population: The safety population was defined as all patients who received at least one dose of any of the 3 study drugs.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone n=6 Participants 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability Any AE	3 participants	6 participants	3 participants	3 participants
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability SAE	3 participants	1 participants	2 participants	2 participants

PRIMARY outcome

Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=52 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=49 Participants 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.
Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone	62 percentage of participants Interval 47.0 to 75.0	—	—	59 percentage of participants Interval 44.0 to 73.0

PRIMARY outcome

Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)

Population: All Phase 1 participants.

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=15 Participants 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.
Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone	—	—	—	2.23 mg/m^2

PRIMARY outcome

Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)

Population: All Phase 1 participants.

MTD of ixazomib will be determined by assessing adverse events and serious adverse events, clinical laboratory values, neurotoxicity grading, and vital sign measurements.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=15 Participants 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.
Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone	—	—	—	2.97 mg/m^2

PRIMARY outcome

Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)

Population: The safety population was defined as all patients who received at least one dose of any of the 3 study drugs.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=53 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=50 Participants 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.
Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation Grade 3 or Higher AEs	75 percentage of participants	—	—	76 percentage of participants
Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation SAEs	43 percentage of participants	—	—	40 percentage of participants
Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation AEs Resulting in Treatment Discontinuation	8 percentage of participants	—	—	8 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1, Days 1 and 15

Population: 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.

Cmax: Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of ixazomib obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone n=4 Participants 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone n=2 Participants 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=2 Participants 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.
Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib Day 1 (n=1, 3, 4, 1)	22.303 ng/mL Standard Deviation 13.0184	94.779 ng/mL Standard Deviation 34.5442	NA ng/mL Standard Deviation NA Not calculated for 1 participant.	NA ng/mL Standard Deviation NA Not calculated for 1 participant.
Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib Day 15 (n=2, 3, 4, 1)	31.368 ng/mL Standard Deviation 31.9963	53.517 ng/mL Standard Deviation 22.1412	NA ng/mL Standard Deviation NA Not calculated for 1 participant.	11.999 ng/mL Standard Deviation NA Not calculated for 2 participants.

SECONDARY outcome

Timeframe: Cycle 1, Days 1 and 15

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone n=4 Participants 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone n=1 Participants 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=2 Participants 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.
Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib Day 15 (n=2, 3, 4, 1)	1.000 hours Interval 0.98 to 2.03	1.015 hours Interval 1.0 to 2.02	2.000 hours Not calculated for 1 participant.	4.165 hours Interval 1.05 to 7.28
Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib Day 1 (n=1, 3, 4, 1)	1.520 hours Interval 1.0 to 8.0	1.060 hours Interval 0.5 to 1.08	0.250 hours Not calculated for 1 participant.	1.020 hours Not calculated for 1 participant.

SECONDARY outcome

Timeframe: Cycle 1, Days 1 and 15

AUC(0-168) is a measure of the area under the plasma concentration-time curve from time 0 to 168 hours postdose for Ixazomib.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone n=4 Participants 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone n=1 Participants 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=2 Participants 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.
Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib Day 15 (n=2, 3, 3, 1)	1083.998 hr*ng/mL Standard Deviation 104.0256	1831.324 hr*ng/mL Standard Deviation 262.7420	NA hr*ng/mL Standard Deviation NA Not calculated for 1 participant.	834.608 hr*ng/mL Standard Deviation NA Not calculated for 2 participants.
Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib Day 1 (n=1, 3, 4, 1)	587.667 hr*ng/mL Standard Deviation 350.1861	923.484 hr*ng/mL Standard Deviation 156.2679	NA hr*ng/mL Standard Deviation NA Not calculated for 1 participant.	NA hr*ng/mL Standard Deviation NA Not calculated for 1 participant.

SECONDARY outcome

Timeframe: Cycle 1, Day 15

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone n=3 Participants 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=1 Participants 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.
Phase 1: Rac: Accumulation Ratio of Ixazomib	1.849 Ratio Standard Deviation 0.8359	2.051 Ratio Standard Deviation 0.6469	—	NA Ratio Standard Deviation NA Not calculated for 1 participant

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of study treatment to the date of first documented progressive disease (Up to 787 days)

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=53 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=50 Participants 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.
Phase 2: Time to Progression (TTP)	NA months Not estimable due to the low number of events.	—	—	NA months Not estimable due to the low number of events.

SECONDARY outcome

Timeframe: From the first dose of study treatment to the date of death (up to 787 days)

Population: 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.

OS was measured as the time in months from the first dose of study treatment to the date of death + 1 day.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=53 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=50 Participants 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.
Phase 2: Overall Survival (OS)	NA participants Not estimable due to the low number of participants who died.	—	—	NA participants Not estimable due to the low number of participants who died.

SECONDARY outcome

Timeframe: Up to 787 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=52 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=49 Participants 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.
Phase 2: Overall Response Rate (ORR)	88 percentage of participants Interval 77.0 to 96.0	—	—	88 percentage of participants Interval 75.0 to 95.0

SECONDARY outcome

Timeframe: After Cycles 3, 6 and 9 (Up to 787 days)

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=52 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=49 Participants 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.
Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After 6 cycles	48 percentage of participants Interval 34.0 to 62.0	—	—	47 percentage of participants Interval 33.0 to 62.0
Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After 3 cycles	37 percentage of participants Interval 24.0 to 51.0	—	—	35 percentage of participants Interval 22.0 to 50.0
Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After 9 cycles	58 percentage of participants Interval 43.0 to 71.0	—	—	57 percentage of participants Interval 42.0 to 71.0

SECONDARY outcome

Timeframe: Cycles 3, 6, 9 and 12 (Up to 787 days)

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=52 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=49 Participants 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.
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) CR	23 percentage of participants Interval 13.0 to 37.0	—	—	20 percentage of participants Interval 10.0 to 34.0
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) sCR	10 percentage of participants Interval 3.0 to 21.0	—	—	6 percentage of participants Interval 1.0 to 17.0
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) VGPR	38 percentage of participants Interval 25.0 to 53.0	—	—	39 percentage of participants Interval 25.0 to 54.0
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) nCR	2 percentage of participants Interval to 10.0 95% CI lower limit is \<1.	—	—	2 percentage of participants Interval to 11.0 95% CI lower limit is \<1.
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) PR	65 percentage of participants Interval 51.0 to 78.0	—	—	67 percentage of participants Interval 52.0 to 80.0
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) MR	6 percentage of participants Interval 1.0 to 16.0	—	—	6 percentage of participants Interval 1.0 to 17.0

SECONDARY outcome

Timeframe: Up to 787 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=46 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=43 Participants 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.
Phase 2: Time to Best Response	3.01 months Interval 0.9 to 12.9	—	—	2.96 months Interval 0.9 to 11.3

SECONDARY outcome

Timeframe: Up to 787 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=52 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=49 Participants 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.
Phase 2: Duration of Response (DOR)	NA months Not estimable due to the low number of participants with events (progressive disease).	—	—	NA months Not estimable due to the low number of participants with events (progressive disease).

SECONDARY outcome

Timeframe: Up to 787 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=53 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=50 Participants 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.
Phase 2: Progression Free Survival (PFS)	NA months Not estimable due to the low number of participants with events.	—	—	14.98 months Interval 13.37 to Not estimable due to the low number of participants with events.

SECONDARY outcome

Timeframe: 1 year after first dose of study drug

1-year survival rate is defined as the percentage of participants still alive at year after the first dose of stud drug.

Outcome measures

Outcome measures
Measure	Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone n=45 Participants 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.	Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone 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.	Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone n=42 Participants 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.
Phase 2: 1 Year Survival Rate	92 percentage of participants Interval 81.0 to 97.0	—	—	92 percentage of participants Interval 80.0 to 97.0

Adverse Events

Phase 1: Ixazomib + Lenalidomide + Dexamethasone

Serious events: 8 serious events

Other events: 15 other events

Deaths: 0 deaths

Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone

Serious events: 20 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director, Clinical Science

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER