Trial Outcomes & Findings for Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis (NCT NCT01318902)

Last Updated: 2020-04-01

Results Overview

An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

Results posted on

2020-04-01

Participant Flow

Participants took part in the study at 9 investigative sites in the United States, Canada, France, Germany and Italy from 27 April 2011 to 13 November 2018.

Participants with previously treated systemic light chain (AL) amyloidosis were enrolled in 2 dose escalation cohorts and were treated with ixazomib 4.0 or 5.5 mg. Participants with relapsed or refractory amyloidosis were enrolled in 2 dose expansion cohorts and treated with ixazomib 4.0 mg in proteosome inhibitor (PI) Naive and PI Exposed groups.

Participant milestones

Participant milestones
Measure	Dose Escalation Cohort: Ixazomib 4.0 mg Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.
Overall Study STARTED	6	5	5	11
Overall Study COMPLETED	5	2	3	5
Overall Study NOT COMPLETED	1	3	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation Cohort: Ixazomib 4.0 mg Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.
Overall Study Symptomatic Deterioration	0	1	1	2
Overall Study Withdrawal by Patient	0	1	0	3
Overall Study Unsatisfactory Therapeutic Response	1	0	0	1
Overall Study Adverse Event	0	1	0	0
Overall Study Terminated by Sponsor	0	0	1	0

Baseline Characteristics

Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=5 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=5 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=11 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Total n=27 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 6.15 • n=93 Participants	69.0 years STANDARD_DEVIATION 8.51 • n=4 Participants	65.8 years STANDARD_DEVIATION 6.26 • n=27 Participants	66.7 years STANDARD_DEVIATION 8.49 • n=483 Participants	66.2 years STANDARD_DEVIATION 7.46 • n=36 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	5 Participants n=483 Participants	13 Participants n=36 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants	6 Participants n=483 Participants	14 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	8 Participants n=483 Participants	22 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	4 Participants n=36 Participants
Race/Ethnicity, Customized White	5 Participants n=93 Participants	5 Participants n=4 Participants	3 Participants n=27 Participants	10 Participants n=483 Participants	23 Participants n=36 Participants
Race/Ethnicity, Customized Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Other	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Height	173.26 cm STANDARD_DEVIATION 7.504 • n=93 Participants	159.17 cm STANDARD_DEVIATION 11.043 • n=4 Participants	173.56 cm STANDARD_DEVIATION 20.728 • n=27 Participants	167.35 cm STANDARD_DEVIATION 9.056 • n=483 Participants	168.30 cm STANDARD_DEVIATION 12.436 • n=36 Participants
Weight	76.78 kg STANDARD_DEVIATION 5.464 • n=93 Participants	64.03 kg STANDARD_DEVIATION 12.664 • n=4 Participants	85.83 kg STANDARD_DEVIATION 40.280 • n=27 Participants	70.96 kg STANDARD_DEVIATION 11.402 • n=483 Participants	73.73 kg STANDARD_DEVIATION 19.536 • n=36 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

Population: Safety population included all participants who received at least 1 dose of ixazomib.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=5 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=11 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=5 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) TEAE	5 Participants	10 Participants	6 Participants	5 Participants
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) SAE	5 Participants	5 Participants	3 Participants	5 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

Population: Safety population included all participants who received at least 1 dose of ixazomib.

The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis. Abnormal laboratory values were assessed as an AE if that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=5 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=11 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=5 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Thrombocytopenia	2 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Anaemia	2 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Neutropenia	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Hyponatraemia	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Hypokalaemia	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Blood creatinine increased	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE Platelet count decreased	0 Participants	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

Population: Safety population included all participants who received at least 1 dose of ixazomib.

Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=5 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=11 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=5 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Number of Participants With Peripheral Neuropathy Reported as a TEAE Peripheral sensory neuropathy	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Peripheral Neuropathy Reported as a TEAE Neuropathy peripheral	0 Participants	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: DLT-evaluable population included all participants who received all Cycle 1 doses of ixazomib or experienced a DLT in Cycle 1.

MTD was highest dose of Ixazomib, at which \<=1 of 6 participants experienced dose-limiting toxicity (DLT). DLT was defined using National Cancer Institute Common Terminology Criteria for Adverse Events, v 4.03 as: Grade 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for \>7 days;Grade 3 neutropenia with fever or infection;Grade 4 thrombocytopenia (platelets \< 25,000/mm\^3) for \>7 days;Grade 3 thrombocytopenia with clinically significant bleeding;platelet count \<10,000/mm\^3;Grade 2 peripheral neuropathy with pain or \>=Grade 3 peripheral neuropathy; \>=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy;Grade 3 QTc prolongation (QTc \>500 msec);any \>=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia;or \<1 week Grade 3 fatigue;delay in initiation of the subsequent therapy cycle by \>2 weeks;other \>=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation, considered possibly related to therapy as assessed by Investigator.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=5 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Maximum Tolerated Dose (MTD) of Ixazomib	—	—	4 mg	4 mg

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: DLT-evaluable population included all participants who received all Cycle 1 doses of ixazomib or experienced a DLT in Cycle 1.

The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1). The RP2D of Ixazomib was determined in dose escalation group on the basis of the totality of safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) data observed in Cycle 1.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=5 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Recommended Phase 2 Dose (RP2D) of Ixazomib	—	—	4 mg	4 mg

SECONDARY outcome

Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Population: Pharmacokinetic (PK) analysis population included all participants who received at least 1 dose of ixazomib and had sufficient ixazomib concentration-time data and dosing data to permit calculation of ixazomib plasma PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=20 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=2 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Cmax: Maximum Observed Plasma Concentration for Ixazomib Cycle 1, Day 1	—	—	54.00 ng/mL Interval 16.7 to 163.0	—
Cmax: Maximum Observed Plasma Concentration for Ixazomib Cycle 1, Day 15	—	—	51.26 ng/mL Interval 10.7 to 131.0	92.20 ng/mL Interval 61.4 to 123.0

SECONDARY outcome

Population: PK analysis population included all participants who received at least 1 dose of ixazomib and had sufficient ixazomib concentration-time data and dosing data to permit calculation of ixazomib plasma PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=20 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=2 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Tmax: Time of First Occurrence of Cmax for Ixazomib Cycle 1, Day 1	—	—	1.0000 hours Interval 0.5 to 2.0	—
Tmax: Time of First Occurrence of Cmax for Ixazomib Cycle 1, Day 15	—	—	1.0000 hours Interval 0.5 to 6.08	0.7500 hours Interval 0.5 to 1.0

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=20 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=2 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib Cycle 1, Day 1	—	—	2.1539 ng/mL Interval 0.0 to 14.4	—
Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib Cycle 1, Day 15	—	—	2.9140 ng/mL Interval 1.01 to 6.75	5.3300 ng/mL Interval 4.41 to 6.25

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=20 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=2 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib Cycle 1, Day 1	—	—	861.0 hr*ng/mL Interval 237.0 to 5010.0	—
AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib Cycle 1, Day 15	—	—	1078.1 hr*ng/mL Interval 465.0 to 2220.0	1725.0 hr*ng/mL Interval 1240.0 to 2210.0

SECONDARY outcome

Population: Pharmacodynamic (PD) analysis population: all participants who received at least 1 dose of ixazomib and had whole blood 20S proteasome inhibition-time data and dosing data to permit calculation of PD parameters. Data was only collected for ixazomib 4.0 mg arm group. Number analyzed is number of participants with evaluable data at given time-point.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=15 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome Cycle 1, Day 15	—	—	61.09 percentage of inhibition Standard Deviation 11.846	—
Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome Cycle 1, Day 1	—	—	54.10 percentage of inhibition Standard Deviation 12.438	—

SECONDARY outcome

Population: PD analysis population: all participants who received at least 1 dose of ixazomib and had whole blood 20S proteasome inhibition-time data and dosing data to permit calculation of PD parameters. Data was only collected for ixazomib 4.0 mg arm group. Number analyzed is number of participants with evaluable data at given time-point.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=15 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib Cycle 1, Day 1	—	—	1.0000 hours Interval 0.5 to 6.0	—
TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib Cycle 1, Day 15	—	—	1.0300 hours Interval 0.5 to 6.02	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=15 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
AUE0-168: Area Under Effect Curve of Whole Blood 20S Proteasome Inhibition From Zero to Concentration at 168 Hours for Ixazomib Cycle 1, Day 1	—	—	3333.6 hr*percentage of inhibition Standard Deviation 1377.24	—
AUE0-168: Area Under Effect Curve of Whole Blood 20S Proteasome Inhibition From Zero to Concentration at 168 Hours for Ixazomib Cycle 1, Day 15	—	—	3943.0 hr*percentage of inhibition Standard Deviation 2322.96	—

SECONDARY outcome

Timeframe: At Cycles 3, 6, 9, and 12; every 6 months thereafter until disease progression or the initiation of subsequent antineoplastic therapy and at end of treatment (EOT) visit (Up to approximately 12 months)

Population: Organ response-evaluable population included all participants who received at least 1 cycle of ixazomib, had amyloid involvement of at least kidney or heart at baseline, and had at least 1 postbaseline organ response assessment.

Organ response rate was estimated as the number of participants with documented organ response (ie. Heart or kidney ). Treatment response of amyloid-related organs were identified based on national cancer institute, common terminology criteria for adverse events (NCI CTCAE) Version 4.02 criteria.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=4 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=8 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=2 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Number of Participants With Best Organ Response to Treatment Based on Investigators Assessment	2 Participants	2 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 22 to 28 in each cycle and end of treatment visit; then every 6 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy (Up to approximately 12 months)

Population: Hematologic response-evaluable population included all participants who received at least 1 cycle of ixazomib, had measureable disease at baseline, and had at least 1 postbaseline hematologic response assessment.

The overall hematologic response rate is defined as number of participants with complete response (CR) or partial response (PR) or very good partial response (VGPR) as assessed by the investigator. Response is determined according to standardized criteria using a central laboratory. CR=serum and urine negative for monoclonal protein by immunofixation; or free light chain ratio normal; \< 5% plasma cells in bone marrow without clonal dominance. PR=reduction in dFLC \> 50%. VGPR= dFLC \< 40 mg/L.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=4 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=11 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=3 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Number of Participants With Best Hematologic Response to Treatment Based on Investigators Assessment	4 Participants	3 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of first documentation of a hematologic response (Up to approximately 12 months)

Population: Hematologic response-evaluable population: all participants who received at least 1 cycle of ixazomib, had measureable disease at baseline, had \>=1 postbaseline hematologic response. No participants had hematologic response for ixazomib 5.5 mg arm group thus were not analyzed. Data is reported for participants evaluable for this outcome measure.

Time to first hematologic response, measured as the time from the first dose of ixazomib to the date of first documentation of a hematologic response.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=4 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=3 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=4 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Time to First Hematologic Response	3.45 months Interval 0.9 to 4.4	2.11 months Interval 1.0 to 3.7	0.79 months Interval 0.7 to 1.8	—

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of first documentation of a organ response (Up to approximately 12 months)

Population: Organ Response-Evaluable population included participants who received at least 1 cycle of ixazomib, who had amyloid involvement of at least kidney or heart at baseline, and who had at least 1 postbaseline organ response assessment.

Time to first organ response, measured as the time from the first dose of ixazomib to the date of first documentation of a organ response.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=2 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=2 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=2 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Time to First Organ Response	9.55 months Interval 2.7 to 16.4	6.85 months Interval 2.5 to 11.2	6.85 months Interval 2.7 to 11.0	—

SECONDARY outcome

Timeframe: From the date of first documentation of a hematologic response to the date of hematologic disease progression (Up to approximately 12 months)

Duration of hematologic response, measured as the time from the date of first documentation of a hematologic response to the date of hematologic disease progression.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=4 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=3 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=4 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Duration of Hematologic Response	69.5 months Interval 7.8 to 75.2	19.7 months Interval 0.4 to 33.2	12.9 months Interval 7.4 to 16.1	—

SECONDARY outcome

Timeframe: From the date of first documentation of a organ response to the date of organ disease progression (Up to approximately 12 months)

Duration of organ response, measured as the time from the date of first documentation of a organ response to the date of organ disease progression.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=1 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=2 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=2 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Duration of Organ Response	20.5 months Interval 20.5 to 20.5	18.25 months Interval 0.0 to 36.5	4.1 months Interval 0.0 to 8.2	—

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of first documented hematologic disease progression (Up to approximately 12 months)

Population: Safety population included all participants who received at least 1 dose of ixazomib. Data is reported for participants evaluable for this outcome measure.

Time to hematologic progression, measured as the time from the date of the first dose of ixazomib to the date of first documented hematologic disease progression.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=2 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=5 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=4 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=1 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Time to Hematologic Disease Progression	73.0 months Interval 0.0 to 78.7	8.3 months Interval 0.9 to 36.8	14.8 months Interval 1.6 to 17.0	NA months Median, lower and upper limit was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of first documented organ disease progression (Up to approximately 12 months)

Time to organ disease progression, measured as the time from the date of the first dose of ixazomib to the date of first documented organ disease progression.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=2 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=2 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=2 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Time to Organ Disease Progression	12.85 months Interval 2.5 to 23.2	25.15 months Interval 2.5 to 47.8	11 months Interval 11.0 to 11.0	—

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to approximately 12 months)

Population: Safety population included all participants who received at least 1 dose of ixazomib. Data is reported for participants evaluable for this outcome measure.

Hematologic disease PFS, measured as the time from the date of the first dose of ixazomib to the date of hematologic disease progression or death.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=3 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=6 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=4 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=3 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Hematologic Disease Progression-Free Survival (PFS)	73.0 months Interval 0.6 to 78.7	8.3 months Interval 0.9 to 36.8	14.8 months Interval 1.6 to 17.0	7.2 months Interval 0.0 to 9.2

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of organ disease progression or death (Up to approximately 12 months)

Organ disease PFS, measured as the time from the date of the first dose of ixazomib to the date of organ disease progression or death.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=4 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=8 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg n=2 Participants Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Organ Disease Progression-Free Survival (PFS)	NA months Data was not estimable due to low number of participants with events.	NA months Data was not estimable due to low number of participants with events.	NA months Data was not estimable due to low number of participants with events.	NA months Data was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to 1 year)

Population: Safety population included all participants who received at least 1 dose of ixazomib.

One-year survival, defined as the patient survival probability at 1 year after the date of first dose of ixazomib.

Outcome measures

Outcome measures
Measure	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) n=5 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) n=11 Participants Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	Dose Escalation Cohort: Ixazomib 4.0 mg n=6 Participants Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.	Dose Escalation Cohort: Ixazomib 5.5 mg Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.
Percentage of Participants With One Year Hematologic Disease PFS	80.0 percentage of participants	21.5 percentage of participants	83.3 percentage of participants	—

Adverse Events

Dose Escalation Cohort: Ixazomib 4.0 mg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Dose Escalation Cohort: Ixazomib 5.5 mg

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)

Serious events: 5 serious events

Other events: 5 other events

Deaths: 1 deaths

Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)

Serious events: 5 serious events

Other events: 10 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 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