Trial Outcomes & Findings for Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral IXAZOMIB in Adult Patients With Relapsed and Refractory Multiple Myeloma (NCT NCT00963820)

Last Updated: 2018-01-10

Results Overview

An Adverse Event 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 (eg, 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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days)

Results posted on

2018-01-10

Participant Flow

Sixty (60) participants took part in the study at 6 investigative sites in the United States from 31 October 2009 to database lock on 28 February 2013.

Participants with a diagnosis of multiple myeloma (relapsed and/or refractory) were enrolled in the dose escalation phase to determine maximum tolerated dose (MTD). Once the MTD was established, participants were enrolled at the MTD into 1 of the 4 expansion cohorts.

Participant milestones

Participant milestones
Measure	0.24 mg/m^2 Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) Ixazomib citrate, 2.97 mg/m\^2 established Maximum Tolerated Dose (MTD), capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Dose Escalation Phase STARTED	3	3	3	3	4	3	8	5	0	0	0	0
Dose Escalation Phase COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Dose Escalation Phase NOT COMPLETED	3	3	3	3	4	3	8	5	0	0	0	0
Expansion Phase STARTED	0	0	0	0	0	0	0	0	11	10	6	4
Expansion Phase COMPLETED	0	0	0	0	0	0	0	0	1	1	1	0
Expansion Phase NOT COMPLETED	0	0	0	0	0	0	0	0	10	9	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	0.24 mg/m^2 Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) Ixazomib citrate, 2.97 mg/m\^2 established Maximum Tolerated Dose (MTD), capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Dose Escalation Phase Progressive Disease	3	3	3	3	4	3	3	2	0	0	0	0
Dose Escalation Phase Adverse Event	0	0	0	0	0	0	3	1	0	0	0	0
Dose Escalation Phase Withdrawal by Subject	0	0	0	0	0	0	1	2	0	0	0	0
Dose Escalation Phase Unsatisfactory Therapeutic Response	0	0	0	0	0	0	1	0	0	0	0	0
Expansion Phase Progressive Disease	0	0	0	0	0	0	0	0	8	6	4	2
Expansion Phase Adverse Event	0	0	0	0	0	0	0	0	1	3	0	0
Expansion Phase Withdrawal by Subject	0	0	0	0	0	0	0	0	1	0	1	1
Expansion Phase Unsatisfactory Therapeutic Response	0	0	0	0	0	0	0	0	0	0	0	1

Baseline Characteristics

Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral IXAZOMIB in Adult Patients With Relapsed and Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=60 Participants Safety Population
Age, Continuous	63.0 years STANDARD_DEVIATION 9.10 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	56 participants n=5 Participants
Race/Ethnicity, Customized Missing	3 participants n=5 Participants
Race/Ethnicity, Customized White	51 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants
Height	168.4 cm STANDARD_DEVIATION 9.34 • n=5 Participants
Weight	83.26 kg STANDARD_DEVIATION 18.106 • n=5 Participants
Body Surface Area at Baseline	1.96 m^2 STANDARD_DEVIATION 0.247 • n=5 Participants

PRIMARY outcome

Timeframe: From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days)

Population: Safety Population included all randomized participants who received study drug.

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=3 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=3 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=3 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=4 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=3 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=8 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=5 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=11 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=10 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=6 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=4 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events	3 participants	3 participants	2 participants	3 participants	4 participants	3 participants	8 participants	5 participants	11 participants	10 participants	6 participants	4 participants

PRIMARY outcome

Timeframe: Cycle 1 Day 1 and End of Study (Up to 354 days)

Population: Safety Population included all randomized participants who received study drug.

Neurotoxicity is graded using participant responses to 11 functional questions on a 5-point scale, where 0=Not at all and 4=Very much, using the Functional Assessment of Cancer Therapy/Gynecology Oncology Group - Neurotoxicity Questionnaire, Version 4.0(14). Neurotoxicity subscale is a sum of 11 reversed item scores where each original score is transformed as (4 - score). The highest possible score is 44, and a higher score indicates more neurotoxicity.

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=3 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=3 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=3 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=4 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=3 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=8 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=5 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=11 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=10 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=6 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=4 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Neurotoxicity Grading Cycle 1 Day 1 (n=2,3,3,3,4,3,7,4,9,8,6,4)	36.00 score on a scale Standard Deviation 9.899	40.33 score on a scale Standard Deviation 1.155	42.00 score on a scale Standard Deviation 3.464	36.00 score on a scale Standard Deviation 7.937	39.50 score on a scale Standard Deviation 2.646	36.80 score on a scale Standard Deviation 4.530	33.14 score on a scale Standard Deviation 7.841	38.50 score on a scale Standard Deviation 4.203	38.44 score on a scale Standard Deviation 5.053	33.73 score on a scale Standard Deviation 6.935	38.00 score on a scale Standard Deviation 6.928	32.00 score on a scale Standard Deviation 8.367
Neurotoxicity Grading End of Study (n=3,3,2,1,1,3,4,3,8,5,4,3)	25.00 score on a scale Standard Deviation 3.606	40.67 score on a scale Standard Deviation 2.517	38.50 score on a scale Standard Deviation 3.536	35.00 score on a scale Standard Deviation 0.000	42.00 score on a scale Standard Deviation 0.000	36.00 score on a scale Standard Deviation 3.606	36.00 score on a scale Standard Deviation 7.528	33.33 score on a scale Standard Deviation 8.386	33.88 score on a scale Standard Deviation 9.219	27.24 score on a scale Standard Deviation 13.122	37.00 score on a scale Standard Deviation 5.944	27.33 score on a scale Standard Deviation 7.371

SECONDARY outcome

Timeframe: Days 1 and 15 of Cycle 1

Population: Participants from the Pharmacokinetic (PK) Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of Cmax.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=3 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=1 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=2 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=3 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=2 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=5 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=4 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=7 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=8 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=5 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Cmax: Maximum Observed Plasma Concentration for MLN2238 Cycle 1 Day 1 (n=1,1,2,1,3,2,5,4,5,8,5,3)	3.010 ng/mL Standard Deviation NA Can not be calculated for 1 participant.	2.91 ng/mL Standard Deviation NA Can not be calculated for 1 participant.	5.75 ng/mL Standard Deviation 4.1083	15.10 ng/mL Standard Deviation NA Can not be calculated for 1 participant.	13.83 ng/mL Standard Deviation 9.7070	29.05 ng/mL Standard Deviation 11.1016	65.46 ng/mL Standard Deviation 29.3351	123.95 ng/mL Standard Deviation 79.2137	75.92 ng/mL Standard Deviation 30.3995	110.43 ng/mL Standard Deviation 62.7006	77.70 ng/mL Standard Deviation 37.9107	83.73 ng/mL Standard Deviation 87.8161
Cmax: Maximum Observed Plasma Concentration for MLN2238 Cycle 1 Day 15 (n=3,1,3,2,2,1,2,1,5,5,4,3)	3.64 ng/mL Standard Deviation 0.9616	4.64 ng/mL Standard Deviation NA Can not be calculated for 1 participant.	6.89 ng/mL Standard Deviation 5.1116	17.90 ng/mL Standard Deviation 8.6267	17.63 ng/mL Standard Deviation 12.6926	9.24 ng/mL Standard Deviation NA Can not be calculated for 1 participant.	100.55 ng/mL Standard Deviation 15.1339	134.00 ng/mL Standard Deviation NA Can not be calculated for 1 participant.	50.46 ng/mL Standard Deviation 22.6877	93.68 ng/mL Standard Deviation 52.7617	118.05 ng/mL Standard Deviation 54.2907	55.10 ng/mL Standard Deviation 41.5275

SECONDARY outcome

Timeframe: Days 1 and 15 of Cycle 1

Population: Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for analysis of Tmax.

Tmax: Time to reach the maximum observed plasma concentration (Cmax), equal to time to Cmax. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=3 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=1 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=2 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=3 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=2 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=5 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=4 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=7 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=8 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=5 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238 Cycle 1 Day 1 (n=1,1,2,1,3,2,5,4,5,8,5,3)	1.50 hours Interval 1.5 to 1.5	1.53 hours Interval 1.53 to 1.53	1.52 hours Interval 1.03 to 2.0	1.00 hours Interval 1.0 to 1.0	1.52 hours Interval 1.0 to 2.0	1.25 hours Interval 1.0 to 1.5	1.00 hours Interval 0.5 to 4.0	1.00 hours Interval 0.53 to 1.5	2.00 hours Interval 0.5 to 2.0	0.50 hours Interval 0.5 to 2.0	1.00 hours Interval 0.5 to 1.42	1.42 hours Interval 1.0 to 1.53
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238 Cycle 1 Day 15 (n=3,1,3,2,2,1,2,1,5,5,4,3)	1.07 hours Interval 1.0 to 2.0	0.50 hours Interval 0.5 to 0.5	1.83 hours Interval 1.0 to 2.0	1.00 hours Interval 1.0 to 1.0	1.27 hours Interval 1.0 to 1.53	8.00 hours Interval 8.0 to 8.0	1.25 hours Interval 0.5 to 2.0	1.03 hours Interval 1.03 to 1.03	1.50 hours Interval 1.0 to 4.03	1.00 hours Interval 0.5 to 1.5	1.00 hours Interval 0.5 to 1.5	1.03 hours Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: Days 1 and 15 of Cycle 1

Population: Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of AUC(0-168).

AUC(0-168) is a measure of the area under the plasma concentration-time curve over the dosing interval (tau) (AUC\[0-tau\]), where tau is the length of the dosing interval - 168 hours in this study). MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=3 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=1 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=2 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=3 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=2 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=5 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=4 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=7 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=8 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=5 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238 Cycle 1 Day 1 (n=0,0,0,0,2,1,3,4,3,5,4,3)	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	258.00 hr*ng/mL Standard Deviation 93.3381	598.00 hr*ng/mL Standard Deviation NA Can not be calculated for 1 participant.	1269.67 hr*ng/mL Standard Deviation 429.3837	1371.25 hr*ng/mL Standard Deviation 725.1939	1793.33 hr*ng/mL Standard Deviation 507.6744	854.20 hr*ng/mL Standard Deviation 330.0745	750.25 hr*ng/mL Standard Deviation 312.3890	813.67 hr*ng/mL Standard Deviation 262.5649
AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238 Cycle 1 Day 15 (n=0,0,2,0,2,1,2,1,1,4,3,2)	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	398.50 hr*ng/mL Standard Deviation 45.9616	NA hr*ng/mL Standard Deviation NA No participants with evaluable data	663.00 hr*ng/mL Standard Deviation 142.8356	868.00 hr*ng/mL Standard Deviation NA Can not be calculated for 1 participant.	3100.00 hr*ng/mL Standard Deviation 834.3860	1460.00 hr*ng/mL Standard Deviation NA Can not be calculated for 1 participant.	3690.00 hr*ng/mL Standard Deviation NA Can not be calculated for 1 participant.	1777.75 hr*ng/mL Standard Deviation 958.4767	1549.00 hr*ng/mL Standard Deviation 1027.6930	2075.00 hr*ng/mL Standard Deviation 1025.3048

SECONDARY outcome

Timeframe: Day 15 of Cycle 1

Population: Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of accumulation ratio.

MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=2 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=1 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=1 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=1 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=1 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=2 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=2 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Accumulation Ratio: Day 15 AUC0-168 / Day 1 AUC0-168 for MLN2238	—	—	—	—	2.64 unitless Standard Deviation 0.3960	1.45 unitless Standard Deviation NA Can not be calculated for 1 participant.	2.25 unitless Standard Deviation NA Can not be calculated for 1 participant.	1.19 unitless Standard Deviation NA Can not be calculated for 1 participant.	2.25 unitless Standard Deviation NA Can not be calculated for 1 participant.	2.19 unitless Standard Deviation 0.8228	1.97 unitless Standard Deviation 0.5869	2.37 unitless Standard Deviation 0.2192

SECONDARY outcome

Timeframe: Day 15 of Cycle 1

Population: Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of terminal elimination rate constant.

Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body and the values were used for calculation of T1/2. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=1 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=2 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=2 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=1 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=1 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=1 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=2 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=4 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=2 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Terminal Elimination Rate Constant (λz) for MLN2238	—	—	0.000 1/hour Standard Deviation NA Can not be calculated for 1 participant.	0.000 1/hour Standard Deviation 0.0001	0.000 1/hour Standard Deviation 0.0003	0.00 1/hour Standard Deviation NA Can not be calculated for 1 participant.	0.00 1/hour Standard Deviation NA Can not be calculated for 1 participant.	0.00 1/hour Standard Deviation NA Can not be calculated for 1 participant.	0.00 1/hour Standard Deviation 0.0019	0.00 1/hour Standard Deviation 0.0014	0.01 1/hour Standard Deviation 0.0019	0.01 1/hour Standard Deviation 0.0003

SECONDARY outcome

Timeframe: Day 15 of Cycle 1

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=1 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=2 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=2 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=1 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=1 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=1 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=2 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=4 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=2 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Terminal Phase Elimination Half-life (T1/2) for MLN2238	—	—	271.00 hour Standard Deviation NA Can not be calculated for 1 participant.	190.50 hour Standard Deviation 7.7782	189.00 hour Standard Deviation 12.7279	175.00 hour Standard Deviation NA Can not be calculated for 1 participant.	246.00 hour Standard Deviation NA Can not be calculated for 1 participant.	165.00 hour Standard Deviation NA Can not be calculated for 1 participant.	186.00 hour Standard Deviation 84.8528	202.33 hour Standard Deviation 63.0899	123.90 hour Standard Deviation 39.4620	108.00 hour Standard Deviation 4.2426

SECONDARY outcome

Timeframe: Days 1 and 15 of Cycle 1

Population: PD analysis Population included all participants who had sufficient dosing data to calculate PD parameters

A Whole Blood 20S Proteasome Inhibition Parameter. There were no subjects in the Pharmacodynamic (PD) Analysis Set for the 2.23 mg/m\^2 cohort, so PD tables do not include that arm.

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=2 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=2 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=3 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=3 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=1 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=5 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=5 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=10 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=8 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=5 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Emax: Maximum Inhibition	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported	NA Percentage of inhibition Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported

SECONDARY outcome

Timeframe: Days 1 and 15 of Cycle 1

Population: PD analysis population included all participants who had sufficient dosing data to calculate PD parameters

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=2 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=2 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=3 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=3 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=3 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=1 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=5 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=5 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=10 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=8 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=5 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=3 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
TEmax: Time of Occurrence of Emax	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.	NA Hours Standard Deviation NA Due to concerns about the third-party laboratory's performance of the 20S assay, accuracy of the data cannot be considered reliable, and therefore, is not being reported.

SECONDARY outcome

Timeframe: Up to 354 days

Population: Response-Evaluable Population included all participants who had measurable disease at Baseline, had received at least 1 dose of study drug, and had at least 1 post-baseline response assessment.

Responses were based on International Myeloma Working Group Uniform Criteria. Complete Response (CR)=Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow. Partial Response (PR)= reduction in M-Protein ≥50% in serum and ≥90% in 24-hour urine. If M-protein unmeasurable, ≥50% decrease in difference of involved and uninvolved Free Light Chain (FLC). If M-protein and FLC unmeasurable, ≥50% reduction in plasma cells is required, if baseline bone marrow plasma cell ≥30%. And ≥50% reduction in the size of soft tissue plasmacytomas. Minimal Response (MR)= 25-49% reduction in serum paraprotein for 6 weeks. 50-89% reduction in 24 hour urinary light chain excretion for 6 weeks. For Non-secretory myeloma patients, 25-49 % reduction in plasma cells in bone marrow and trephine biopsy for a 6 weeks. 25-49% reduction in the size of soft tissue plasmacytomas. No increase in the size or number of lytic bone lesions.

Outcome measures

Outcome measures
Measure	0.24 mg/m^2 n=2 Participants Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.48 mg/m^2 n=3 Participants Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	0.80 mg/m^2 n=2 Participants Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.20 mg/m^2 n=3 Participants Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	1.68 mg/m^2 n=2 Participants Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.23 mg/m^2 n=3 Participants Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	2.97 mg/m^2 n=4 Participants Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	3.95 mg/m^2 n=4 Participants Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Relapsed and Refractory (RR) n=11 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	VELCADE-relapsed (VR) n=9 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m\^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	PI naïve n=6 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.	Carfilzomib n=4 Participants Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time CR + PR	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	25 percentage of participants Interval 0.0 to 81.0	25 percentage of participants Interval 0.0 to 81.0	9 percentage of participants Interval 0.0 to 41.0	22 percentage of participants Interval 3.0 to 60.0	17 percentage of participants Interval 0.0 to 64.0	25 percentage of participants Interval 0.0 to 81.0
Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time CR + PR + MR	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 0.0	25 percentage of participants Interval 0.0 to 81.0	25 percentage of participants Interval 0.0 to 81.0	18 percentage of participants Interval 2.0 to 52.0	33 percentage of participants Interval 7.0 to 70.0	17 percentage of participants Interval 0.0 to 64.0	25 percentage of participants Interval 0.0 to 81.0

Adverse Events

Dose Escalation Cohorts

Serious events: 7 serious events

Other events: 30 other events

Deaths: 0 deaths

Expansion Cohorts

Serious events: 15 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator may publish clinical data after the earlier of publication by Sponsor or 12 months after early termination or database lock. Proposed publication copy should be provided to Sponsor at least 30 days prior to submission/disclosure. If requested, Sponsor's confidential information must be removed and publication delayed if Sponsor intends to file a related patent application.
Publication restrictions are in place

Restriction type: OTHER