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

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01318902
• Collaborator: (none)
• Enrollment: 27
• Locations: 10
• Arms: 4
• Actual Duration (Months): 90.6
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will include participants with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who require further therapy and will be aimed at determining the safety profile and the maximum tolerated dose/recommended phase 2 dose of MLN9078 (Ixazomib) administered orally.

Condition or Disease	Intervention/Treatment	Phase
Light-Chain Amyloidosis	Drug: Ixazomib; Drug: Dexamethasone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Formulation of MLN9708 Administered Weekly in Adult Patients With Relapsed or Refractory Light-Chain (AL) Amyloidosis Who Require Further Treatment
• Actual Study Start Date: Apr 27, 2011
• Actual Primary Completion Date: Nov 13, 2018
• Actual Study Completion Date: Nov 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Ixazomib; Ixazomib capsules.; Other Names: MLN9708 ; Drug: Dexamethasone; Dexamethasone tablets.
Experimental: 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.	Drug: Ixazomib; Ixazomib capsules.; Other Names: MLN9708 ; Drug: Dexamethasone; Dexamethasone tablets.
Experimental: 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.	Drug: Ixazomib; Ixazomib capsules.; Other Names: MLN9708
Experimental: 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.	Drug: Ixazomib; Ixazomib capsules.; Other Names: MLN9708

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) [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)]

   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.

2. Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE [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)]

   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.

3. Number of Participants With Peripheral Neuropathy Reported as a TEAE [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)]

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

4. Maximum Tolerated Dose (MTD) of Ixazomib [Cycle 1 (28 days)]

   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.

5. Recommended Phase 2 Dose (RP2D) of Ixazomib [Cycle 1 (28 days)]

   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.

Secondary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration for Ixazomib [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]

2. Tmax: Time of First Occurrence of Cmax for Ixazomib [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]

3. Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib [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]

4. AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib [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]

5. Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome [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]

6. TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib [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]

7. 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 (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]

8. Number of Participants With Best Organ Response to Treatment Based on Investigators Assessment [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)]

   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.

9. Number of Participants With Best Hematologic Response to Treatment Based on Investigators Assessment [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)]

   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.

10. Time to First Hematologic Response [From the date of the first dose of ixazomib to the date of first documentation of a hematologic response (Up to approximately 12 months)]

    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.

11. Time to First Organ Response [From the date of the first dose of ixazomib to the date of first documentation of a organ response (Up to approximately 12 months)]

    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.

12. Duration of Hematologic Response [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.

13. Duration of Organ Response [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.

14. Time to Hematologic Disease Progression [From the date of the first dose of ixazomib to the date of first documented hematologic disease progression (Up to approximately 12 months)]

    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.

15. Time to Organ Disease Progression [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.

16. Hematologic Disease Progression-Free Survival (PFS) [From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to approximately 12 months)]

    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.

17. Organ Disease Progression-Free Survival (PFS) [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.

18. Percentage of Participants With One Year Hematologic Disease PFS [From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to 1 year)]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participants 18 years or older

• Biopsy-proven systemic relapsed or refractory light-chain (AL) amyloidosis, which after at least 1 prior therapy, in the investigator's opinion, requires further treatment

• If received stem cell transplant, must be at least 3 months posttransplantation and recovered from side effects

• Must have measurable disease defined as serum differential free light chain concentration ≥ 40 mg/L

• Must have objective measurable organ (heart or kidney) amyloid involvement

• Must have cardiac biomarker risk stage I or II disease

• Must have adequate hematologic, hepatic, and renal function

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• Female participants who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse

• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse

• Voluntary written consent

Exclusion Criteria

• Peripheral neuropathy that is greater or equal to Grade 2

• Cardiac status as described in protocol

• Severe diarrhea (≥ Grade 3) not controllable with medication or requires administration of total parenteral nutrition

• Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708

• Uncontrolled infection requiring systematic antibiotics

• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection

• Presence of other active malignancy with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate-specific antigen is within normal limit, or any completely resected carcinoma in situ

• Female participants who are lactating or pregnant

• Major surgery within 14 days before the first dose of study drug

• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts Medical Center	Boston	Massachusetts	United States	02111
2	Boston Medical Center	Boston	Massachusetts	United States	02118
3	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Mount Sinai Medical Center	New York	New York	United States	10029
6	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
7	University Health Network	Toronto	Ontario	Canada	M5G 2M9
8	CHU Limoges, Department of Hematology and Cell Therapy, Reference Center for AL amyloidosis	Limoges Cedex		France	87042
9	Universitatsklinikum Heidelberg Innere Medizin V; Hamatologie, Onkologie und Rheumatologie	Heidelberg		Germany	D-69120
10	Amyloidosis Research & Treatment Center, Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 6, 2012
• Study Protocol - Dec 22, 2014

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01318902
• Other Study ID Numbers: C16007; 2010-022497-13; U1111-1168-1192
• First Posted: Mar 21, 2011
• Last Update Posted: Apr 1, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Millennium Pharmaceuticals, Inc.: Drug therapy
• Additional relevant MeSH terms: Amyloidosis; Dexamethasone; Ixazomib

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
STARTED	6	5	5	11
COMPLETED	5	2	3	5
NOT COMPLETED	1	3	2	6

Baseline Characteristics

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)	Total
Arm/Group Description	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.	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.	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.	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 of all reporting groups
Overall Participants	6	5	5	11	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.3 (6.15)	69.0 (8.51)	65.8 (6.26)	66.7 (8.49)	66.2 (7.46)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	4 80%	2 40%	5 45.5%	13 48.1%
Male	4 66.7%	1 20%	3 60%	6 54.5%	14 51.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	1 9.1%	1 3.7%
Not Hispanic or Latino	5 83.3%	4 80%	5 100%	8 72.7%	22 81.5%
Unknown or Not Reported	1 16.7%	1 20%	0 0%	2 18.2%	4 14.8%
Race/Ethnicity, Customized (Count of Participants)
White	5 83.3%	5 100%	3 60%	10 90.9%	23 85.2%
Asian	0 0%	0 0%	1 20%	0 0%	1 3.7%
Black or African American	0 0%	0 0%	1 20%	0 0%	1 3.7%
Not Reported	0 0%	0 0%	0 0%	1 9.1%	1 3.7%
Other	1 16.7%	0 0%	0 0%	0 0%	1 3.7%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.26 (7.504)	159.17 (11.043)	173.56 (20.728)	167.35 (9.056)	168.30 (12.436)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	76.78 (5.464)	64.03 (12.664)	85.83 (40.280)	70.96 (11.402)	73.73 (19.536)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	5	5	11
TEAE	6 100%	5 100%	5 100%	10 90.9%
SAE	3 50%	5 100%	5 100%	5 45.5%

2. Primary Outcome

Title	Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	5	5	11
Thrombocytopenia	2 33.3%	0 0%	2 40%	2 18.2%
Anaemia	2 33.3%	0 0%	2 40%	0 0%
Neutropenia	0 0%	0 0%	0 0%	1 9.1%
Hyponatraemia	1 16.7%	0 0%	1 20%	1 9.1%
Hypokalaemia	1 16.7%	0 0%	0 0%	1 9.1%
Blood creatinine increased	1 16.7%	0 0%	0 0%	1 9.1%
Platelet count decreased	0 0%	2 40%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Peripheral Neuropathy Reported as a TEAE
Description	Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	5	5	11
Peripheral sensory neuropathy	1 16.7%	0 0%	1 20%	1 9.1%
Neuropathy peripheral	1 16.7%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Ixazomib
Description	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.
Time Frame	Cycle 1 (28 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg
Arm/Group Description	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.	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.
Measure Participants	6	5
Number [mg]	4	4

5. Primary Outcome

Title	Recommended Phase 2 Dose (RP2D) of Ixazomib
Description	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.
Time Frame	Cycle 1 (28 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg
Arm/Group Description	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.	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.
Measure Participants	6	5
Number [mg]	4	4

6. Secondary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg	Ixazomib 5.5 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	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 was added on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. The maximum duration of treatment was up to 12 cycles.
Measure Participants	20	2
Cycle 1, Day 1	54.00
Cycle 1, Day 15	51.26	92.20

7. Secondary Outcome

Title	Tmax: Time of First Occurrence of Cmax for Ixazomib
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg	Ixazomib 5.5 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	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 was added on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. The maximum duration of treatment was up to 12 cycles.
Measure Participants	20	2
Cycle 1, Day 1	1.0000
Cycle 1, Day 15	1.0000	0.7500

8. Secondary Outcome

Title	Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg	Ixazomib 5.5 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	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 was added on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. The maximum duration of treatment was up to 12 cycles.
Measure Participants	20	2
Cycle 1, Day 1	2.1539
Cycle 1, Day 15	2.9140	5.3300

9. Secondary Outcome

Title	AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg	Ixazomib 5.5 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.	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 was added on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. The maximum duration of treatment was up to 12 cycles.
Measure Participants	20	2
Cycle 1, Day 1	861.0
Cycle 1, Day 15	1078.1	1725.0

10. Secondary Outcome

Title	Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.
Measure Participants	15
Cycle 1, Day 1	54.10 (12.438)
Cycle 1, Day 15	61.09 (11.846)

11. Secondary Outcome

Title	TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.
Measure Participants	15
Cycle 1, Day 1	1.0000
Cycle 1, Day 15	1.0300

12. Secondary Outcome

Title	AUE0-168: Area Under Effect Curve of Whole Blood 20S Proteasome Inhibition From Zero to Concentration at 168 Hours for Ixazomib
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixazomib 4.0 mg
Arm/Group Description	Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1 and 15 during each 28-day treatment cycle for all the participants from dose escalation and expansion cohorts were evaluated in this arm group. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.
Measure Participants	15
Cycle 1, Day 1	3333.6 (1377.24)
Cycle 1, Day 15	3943.0 (2322.96)

13. Secondary Outcome

Title	Number of Participants With Best Organ Response to Treatment Based on Investigators Assessment
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	2	4	8
Count of Participants [Participants]	2 33.3%	0 0%	2 40%	2 18.2%

14. Secondary Outcome

Title	Number of Participants With Best Hematologic Response to Treatment Based on Investigators Assessment
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	3	4	11
Count of Participants [Participants]	4 66.7%	0 0%	4 80%	3 27.3%

15. Secondary Outcome

Title	Time to First Hematologic Response
Description	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.
Time Frame	From the date of the first dose of ixazomib to the date of first documentation of a hematologic response (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	4	0	4	3
Median (Full Range) [months]	0.79	3.45	2.11

16. Secondary Outcome

Title	Time to First Organ Response
Description	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.
Time Frame	From the date of the first dose of ixazomib to the date of first documentation of a organ response (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	0	2	2
Median (Full Range) [months]	6.85	9.55	6.85

17. Secondary Outcome

Title	Duration of Hematologic Response
Description	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.
Time Frame	From the date of first documentation of a hematologic response to the date of hematologic disease progression (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	4	0	4	3
Median (Full Range) [months]	12.9	69.5	19.7

18. Secondary Outcome

Title	Duration of Organ Response
Description	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.
Time Frame	From the date of first documentation of a organ response to the date of organ disease progression (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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. Number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	0	1	2
Median (Full Range) [months]	4.1	20.5	18.25

19. Secondary Outcome

Title	Time to Hematologic Disease Progression
Description	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.
Time Frame	From the date of the first dose of ixazomib to the date of first documented hematologic disease progression (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	4	1	2	5
Median (Full Range) [months]	14.8	NA	73.0	8.3

20. Secondary Outcome

Title	Time to Organ Disease Progression
Description	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.
Time Frame	From the date of the first dose of ixazomib to the date of first documented organ disease progression (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	0	2	2
Median (Full Range) [months]	11	12.85	25.15

21. Secondary Outcome

Title	Hematologic Disease Progression-Free Survival (PFS)
Description	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.
Time Frame	From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	4	3	3	6
Median (Full Range) [months]	14.8	7.2	73.0	8.3

22. Secondary Outcome

Title	Organ Disease Progression-Free Survival (PFS)
Description	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.
Time Frame	From the date of the first dose of ixazomib to the date of organ disease progression or death (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	2	4	8
Median (Full Range) [months]	NA	NA	NA	NA

23. Secondary Outcome

Title	Percentage of Participants With One Year Hematologic Disease PFS
Description	One-year survival, defined as the patient survival probability at 1 year after the date of first dose of ixazomib.
Time Frame	From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to 1 year)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg	Dose Escalation Cohort: Ixazomib 5.5 mg	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)	Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	6	0	5	11
Number [percentage of participants]	83.3 1388.3%	80.0 1600%	21.5 430%

Adverse Events

Time Frame	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)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Dose Escalation Cohort: Ixazomib 4.0 mg		Dose Escalation Cohort: Ixazomib 5.5 mg		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Dose Escalation Cohort: Ixazomib 4.0 mg		Dose Escalation Cohort: Ixazomib 5.5 mg		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Serious Adverse Events
	Dose Escalation Cohort: Ixazomib 4.0 mg		Dose Escalation Cohort: Ixazomib 5.5 mg		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		5/5 (100%)		5/5 (100%)		5/11 (45.5%)
Cardiac disorders
Atrial fibrillation	0/6 (0%)		2/5 (40%)		0/5 (0%)		0/11 (0%)
Cardiac failure congestive	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Angina pectoris	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Cardiac arrest	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Cardiac failure	0/6 (0%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Abdominal pain	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Diarrhoea	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Nausea	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/11 (0%)
General disorders
Facial pain	0/6 (0%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Hepatobiliary disorders
Cholecystitis	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Infections and infestations
Pneumonia	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Influenza	0/6 (0%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Injury, poisoning and procedural complications
Fall	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Metabolism and nutrition disorders
Dehydration	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/11 (0%)
Hyperkalaemia	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Hypokalaemia	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/11 (0%)
Hyponatraemia	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/11 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Plasmacytoma	0/6 (0%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Squamous cell carcinoma of skin	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Nervous system disorders
Presyncope	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Renal and urinary disorders
Acute kidney injury	0/6 (0%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Renal failure	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/6 (16.7%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Dyspnoea	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Haemothorax	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Hypoxia	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Respiratory failure	0/6 (0%)		1/5 (20%)		0/5 (0%)		0/11 (0%)
Vascular disorders
Hypotension	0/6 (0%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Dose Escalation Cohort: Ixazomib 4.0 mg		Dose Escalation Cohort: Ixazomib 5.5 mg		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)		Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		5/5 (100%)		5/5 (100%)		10/11 (90.9%)
Blood and lymphatic system disorders
Thrombocytopenia	2/6 (33.3%)		0/5 (0%)		2/5 (40%)		2/11 (18.2%)
Anaemia	2/6 (33.3%)		0/5 (0%)		2/5 (40%)		0/11 (0%)
Increased tendency to bruise	0/6 (0%)		0/5 (0%)		2/5 (40%)		1/11 (9.1%)
Neutropenia	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Cardiac disorders
Cardiac failure	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Angina pectoris	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Atrial flutter	0/6 (0%)		1/5 (20%)		1/5 (20%)		0/11 (0%)
Eye disorders
Conjunctivitis	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Dry eye	0/6 (0%)		0/5 (0%)		2/5 (40%)		0/11 (0%)
Ocular hyperaemia	0/6 (0%)		0/5 (0%)		2/5 (40%)		0/11 (0%)
Gastrointestinal disorders
Nausea	4/6 (66.7%)		4/5 (80%)		3/5 (60%)		4/11 (36.4%)
Diarrhoea	3/6 (50%)		3/5 (60%)		3/5 (60%)		5/11 (45.5%)
Constipation	1/6 (16.7%)		3/5 (60%)		2/5 (40%)		2/11 (18.2%)
Vomiting	1/6 (16.7%)		2/5 (40%)		1/5 (20%)		1/11 (9.1%)
Abdominal pain	1/6 (16.7%)		2/5 (40%)		0/5 (0%)		1/11 (9.1%)
Abdominal distension	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Abdominal pain upper	0/6 (0%)		0/5 (0%)		0/5 (0%)		2/11 (18.2%)
Dry mouth	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Dyspepsia	0/6 (0%)		0/5 (0%)		0/5 (0%)		2/11 (18.2%)
General disorders
Fatigue	2/6 (33.3%)		3/5 (60%)		3/5 (60%)		6/11 (54.5%)
Pyrexia	1/6 (16.7%)		1/5 (20%)		1/5 (20%)		5/11 (45.5%)
Oedema peripheral	3/6 (50%)		0/5 (0%)		2/5 (40%)		2/11 (18.2%)
Asthenia	0/6 (0%)		1/5 (20%)		0/5 (0%)		5/11 (45.5%)
Chills	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Gait disturbance	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Influenza like illness	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Infections and infestations
Upper respiratory tract infection	2/6 (33.3%)		0/5 (0%)		3/5 (60%)		2/11 (18.2%)
Cellulitis	0/6 (0%)		0/5 (0%)		2/5 (40%)		1/11 (9.1%)
Nasopharyngitis	0/6 (0%)		0/5 (0%)		2/5 (40%)		1/11 (9.1%)
Bronchitis	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Injury, poisoning and procedural complications
Contusion	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		2/11 (18.2%)
Fall	0/6 (0%)		0/5 (0%)		1/5 (20%)		2/11 (18.2%)
Investigations
Blood creatinine increased	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Platelet count decreased	0/6 (0%)		2/5 (40%)		0/5 (0%)		0/11 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/6 (33.3%)		2/5 (40%)		1/5 (20%)		3/11 (27.3%)
Fluid retention	0/6 (0%)		1/5 (20%)		0/5 (0%)		2/11 (18.2%)
Hyponatraemia	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Dehydration	0/6 (0%)		1/5 (20%)		1/5 (20%)		0/11 (0%)
Hyperglycaemia	0/6 (0%)		0/5 (0%)		2/5 (40%)		0/11 (0%)
Hypokalaemia	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)
Musculoskeletal and connective tissue disorders
Pain in extremity	3/6 (50%)		0/5 (0%)		0/5 (0%)		3/11 (27.3%)
Muscular weakness	0/6 (0%)		0/5 (0%)		2/5 (40%)		3/11 (27.3%)
Back pain	0/6 (0%)		0/5 (0%)		1/5 (20%)		3/11 (27.3%)
Arthralgia	0/6 (0%)		0/5 (0%)		1/5 (20%)		2/11 (18.2%)
Muscle spasms	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Myalgia	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Nervous system disorders
Headache	1/6 (16.7%)		0/5 (0%)		2/5 (40%)		2/11 (18.2%)
Dizziness	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		2/11 (18.2%)
Dysgeusia	1/6 (16.7%)		0/5 (0%)		2/5 (40%)		1/11 (9.1%)
Peripheral sensory neuropathy	1/6 (16.7%)		0/5 (0%)		2/5 (40%)		1/11 (9.1%)
Neuropathy peripheral	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Paraesthesia	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Psychiatric disorders
Insomnia	1/6 (16.7%)		1/5 (20%)		2/5 (40%)		2/11 (18.2%)
Mood altered	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/6 (16.7%)		2/5 (40%)		3/5 (60%)		2/11 (18.2%)
Cough	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		2/11 (18.2%)
Nasal congestion	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Oropharyngeal pain	1/6 (16.7%)		0/5 (0%)		2/5 (40%)		0/11 (0%)
Epistaxis	0/6 (0%)		0/5 (0%)		0/5 (0%)		2/11 (18.2%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/6 (16.7%)		1/5 (20%)		2/5 (40%)		2/11 (18.2%)
Pruritus	0/6 (0%)		1/5 (20%)		2/5 (40%)		2/11 (18.2%)
Dry skin	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Rash macular	0/6 (0%)		0/5 (0%)		1/5 (20%)		1/11 (9.1%)
Rash pruritic	0/6 (0%)		0/5 (0%)		0/5 (0%)		2/11 (18.2%)
Skin lesion	1/6 (16.7%)		0/5 (0%)		1/5 (20%)		0/11 (0%)
Vascular disorders
Hypotension	1/6 (16.7%)		1/5 (20%)		1/5 (20%)		3/11 (27.3%)
Hypertension	1/6 (16.7%)		0/5 (0%)		0/5 (0%)		1/11 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.