Trial Outcomes & Findings for Ixazomib Citrate, Lenalidomide, Dexamethasone, and Daratumumab in Treating Patients With Newly Diagnosed Multiple Myeloma (NCT NCT03012880)

NCT ID: NCT03012880

Last Updated: 2025-06-04

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

2 years

Results posted on

2025-06-04

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	40	40
Overall Study COMPLETED	38	40
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Overall Study Withdrawal by Subject	1	0
Overall Study Ineligible	1	0

Baseline Characteristics

Ixazomib Citrate, Lenalidomide, Dexamethasone, and Daratumumab in Treating Patients With Newly Diagnosed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Total n=78 Participants Total of all reporting groups
Age, Continuous	62 years n=99 Participants	64.5 years n=107 Participants	63.5 years n=206 Participants
Sex: Female, Male Female	20 Participants n=99 Participants	15 Participants n=107 Participants	35 Participants n=206 Participants
Sex: Female, Male Male	18 Participants n=99 Participants	25 Participants n=107 Participants	43 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=99 Participants	36 Participants n=107 Participants	72 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	37 Participants n=99 Participants	38 Participants n=107 Participants	75 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Proportion of Patients Who Achieve a Confirmed Complete Response (CR)	0.32 proportion of participants Interval 0.184 to 0.474	0.30 proportion of participants Interval 0.175 to 0.475

SECONDARY outcome

Timeframe: 2 years

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables are in the adverse event section of this report. The rate of patients that suffered a grade 3 or higher adverse event are reported here.

Outcome measures

Outcome measures
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Proportion of Patients That Experienced a Grade 3 or Higher Adverse Event.	0.58 proportion of participants	0.53 proportion of participants

SECONDARY outcome

Timeframe: 2 years

Will be estimated by the number of patients who achieve a stringent complete response (sCR), CR, VGPR or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.

Outcome measures

Outcome measures
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Overall Response Rate (ORR)	0.97 proportion of participants Interval 0.87 to 1.0	0.95 proportion of participants Interval 0.83 to 1.0

SECONDARY outcome

Timeframe: 2 years

The distribution of overall survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS)	NA Months Too few events observed, can't calculate median or limits.	NA Months Too few events observed, can't calculate median or limits.

SECONDARY outcome

Timeframe: 2 years

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Progression Free Survival	NA Months Too few events observed, can't calculate median or limits.	NA Months Too few events observed, can't calculate median or limits.

SECONDARY outcome

Timeframe: 2 years

Will be estimated by the number of patients with a VGPR, CR, or Stringent Complete Response (sCR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.

Outcome measures

Outcome measures
Measure	Cohort A n=38 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 Participants INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.\> \> MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Rate of >= Very Good Partial Response (VGPR)	0.74 proportion of participants Interval 0.58 to 0.87	0.68 proportion of participants Interval 0.5 to 0.83

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 2 years

Will be assessed on bone marrow aspirate in all patients achieving CR. The proportion of patients who achieve MRD negative status will be estimated by the number of patients who are MRD negative divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 2 years

The FACT/GOG neurotoxicity questionnaire will be completed. Patients will be evaluated by overall score for each questionnaire at each time point and changes over time will be calculated. These measures will be correlated with outcome using Fisher's exact test and Kaplan-Meier methods where appropriate.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A

Serious events: 10 serious events

Other events: 39 other events

Deaths: 4 deaths

Cohort B

Serious events: 8 serious events

Other events: 40 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Shaji Kumar

Mayo Clinic

Phone: 507-284-5096

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A n=39 participants at risk MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 participants at risk MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Cardiac disorders Atrial fibrillation	5.1% 2/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Eye disorders Glaucoma	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Diarrhea	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Ileus	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
General disorders Fatigue	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
General disorders Fever	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
General disorders Flu like symptoms	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
General disorders Multi-organ failure	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Infections and infestations Appendicitis	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Infections and infestations Infections and infestations - Oth spec	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Infections and infestations Lung infection	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	5.0% 2/40 • Number of events 3 • 2 years All registered patients that were evaluated are included.
Infections and infestations Sepsis	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Infections and infestations Upper respiratory infection	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Infections and infestations Urinary tract infection	7.7% 3/39 • Number of events 3 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Investigations Creatinine increased	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Investigations Urine output decreased	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Metabolism and nutrition disorders Dehydration	5.1% 2/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Metabolism and nutrition disorders Hypocalcemia	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Metabolism and nutrition disorders Hypokalemia	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Somnolence	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Syncope	5.1% 2/39 • Number of events 3 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Psychiatric disorders Confusion	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Renal and urinary disorders Acute kidney injury	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.1% 2/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Vascular disorders Hypotension	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Vascular disorders Thromboembolic event	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.

Measure	Cohort A n=39 participants at risk MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.	Cohort B n=40 participants at risk MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	10.3% 4/39 • Number of events 9 • 2 years All registered patients that were evaluated are included.	20.0% 8/40 • Number of events 25 • 2 years All registered patients that were evaluated are included.
Blood and lymphatic system disorders Lymph node pain	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Cardiac disorders Atrial fibrillation	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Eye disorders Blurred vision	5.1% 2/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Eye disorders Cataract	2.6% 1/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Eye disorders Eye disorders - Other, specify	2.6% 1/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Constipation	7.7% 3/39 • Number of events 4 • 2 years All registered patients that were evaluated are included.	15.0% 6/40 • Number of events 21 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Dental caries	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Diarrhea	61.5% 24/39 • Number of events 212 • 2 years All registered patients that were evaluated are included.	60.0% 24/40 • Number of events 230 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Gastrointestinal disorders - Oth spec	2.6% 1/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Nausea	61.5% 24/39 • Number of events 122 • 2 years All registered patients that were evaluated are included.	52.5% 21/40 • Number of events 167 • 2 years All registered patients that were evaluated are included.
Gastrointestinal disorders Vomiting	35.9% 14/39 • Number of events 33 • 2 years All registered patients that were evaluated are included.	32.5% 13/40 • Number of events 53 • 2 years All registered patients that were evaluated are included.
General disorders Edema limbs	7.7% 3/39 • Number of events 5 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 4 • 2 years All registered patients that were evaluated are included.
General disorders Fatigue	100.0% 39/39 • Number of events 614 • 2 years All registered patients that were evaluated are included.	95.0% 38/40 • Number of events 499 • 2 years All registered patients that were evaluated are included.
General disorders Pain	5.1% 2/39 • Number of events 6 • 2 years All registered patients that were evaluated are included.	5.0% 2/40 • Number of events 3 • 2 years All registered patients that were evaluated are included.
Infections and infestations Infections and infestations - Oth spec	10.3% 4/39 • Number of events 13 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Infections and infestations Lung infection	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	5.0% 2/40 • Number of events 3 • 2 years All registered patients that were evaluated are included.
Infections and infestations Mucosal infection	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Infections and infestations Sepsis	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Infections and infestations Sinusitis	5.1% 2/39 • Number of events 11 • 2 years All registered patients that were evaluated are included.	10.0% 4/40 • Number of events 5 • 2 years All registered patients that were evaluated are included.
Infections and infestations Upper respiratory infection	23.1% 9/39 • Number of events 17 • 2 years All registered patients that were evaluated are included.	37.5% 15/40 • Number of events 21 • 2 years All registered patients that were evaluated are included.
Infections and infestations Urinary tract infection	20.5% 8/39 • Number of events 10 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Injury, poisoning and procedural complications Fall	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Injury, poisoning and procedural complications Fracture	5.1% 2/39 • Number of events 4 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Injury, poisoning and procedural complications Infusion related reaction	20.5% 8/39 • Number of events 8 • 2 years All registered patients that were evaluated are included.	25.0% 10/40 • Number of events 10 • 2 years All registered patients that were evaluated are included.
Investigations CD4 lymphocytes decreased	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Investigations Creatinine increased	20.5% 8/39 • Number of events 60 • 2 years All registered patients that were evaluated are included.	37.5% 15/40 • Number of events 113 • 2 years All registered patients that were evaluated are included.
Investigations Lymphocyte count decreased	56.4% 22/39 • Number of events 265 • 2 years All registered patients that were evaluated are included.	67.5% 27/40 • Number of events 282 • 2 years All registered patients that were evaluated are included.
Investigations Lymphocyte count increased	10.3% 4/39 • Number of events 5 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Investigations Neutrophil count decreased	79.5% 31/39 • Number of events 122 • 2 years All registered patients that were evaluated are included.	55.0% 22/40 • Number of events 81 • 2 years All registered patients that were evaluated are included.
Investigations Platelet count decreased	59.0% 23/39 • Number of events 149 • 2 years All registered patients that were evaluated are included.	55.0% 22/40 • Number of events 112 • 2 years All registered patients that were evaluated are included.
Investigations White blood cell decreased	15.4% 6/39 • Number of events 15 • 2 years All registered patients that were evaluated are included.	37.5% 15/40 • Number of events 50 • 2 years All registered patients that were evaluated are included.
Metabolism and nutrition disorders Anorexia	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Metabolism and nutrition disorders Hyperglycemia	2.6% 1/39 • Number of events 2 • 2 years All registered patients that were evaluated are included.	12.5% 5/40 • Number of events 18 • 2 years All registered patients that were evaluated are included.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	5.0% 2/40 • Number of events 2 • 2 years All registered patients that were evaluated are included.
Musculoskeletal and connective tissue disorders Back pain	5.1% 2/39 • Number of events 3 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Musculoskeletal and connective tissue disorders Musculoskeletal, conn tissue - Oth spec	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 2/39 • Number of events 8 • 2 years All registered patients that were evaluated are included.	7.5% 3/40 • Number of events 11 • 2 years All registered patients that were evaluated are included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mal, uncpec - Oth spec	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	5.0% 2/40 • Number of events 3 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Nervous system disorders - Oth spec	2.6% 1/39 • Number of events 5 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Peripheral motor neuropathy	28.2% 11/39 • Number of events 69 • 2 years All registered patients that were evaluated are included.	7.5% 3/40 • Number of events 60 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Peripheral sensory neuropathy	82.1% 32/39 • Number of events 406 • 2 years All registered patients that were evaluated are included.	70.0% 28/40 • Number of events 392 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Presyncope	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 3 • 2 years All registered patients that were evaluated are included.
Nervous system disorders Tremor	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 2 • 2 years All registered patients that were evaluated are included.
Psychiatric disorders Anxiety	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 2 • 2 years All registered patients that were evaluated are included.
Psychiatric disorders Insomnia	17.9% 7/39 • Number of events 15 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Reproductive system and breast disorders Erectile dysfunction	5.1% 2/39 • Number of events 4 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Respiratory, thoracic and mediastinal disorders Resp, thoracic, mediastinal - Oth spec	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	5.0% 2/40 • Number of events 2 • 2 years All registered patients that were evaluated are included.
Skin and subcutaneous tissue disorders Rash maculo-papular	48.7% 19/39 • Number of events 46 • 2 years All registered patients that were evaluated are included.	55.0% 22/40 • Number of events 71 • 2 years All registered patients that were evaluated are included.
Skin and subcutaneous tissue disorders Skin and subcut tissue disord - Oth spec	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Skin and subcutaneous tissue disorders Skin ulceration	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	0.00% 0/40 • 2 years All registered patients that were evaluated are included.
Vascular disorders Hypertension	2.6% 1/39 • Number of events 1 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Vascular disorders Lymphocele	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 1 • 2 years All registered patients that were evaluated are included.
Vascular disorders Thromboembolic event	0.00% 0/39 • 2 years All registered patients that were evaluated are included.	2.5% 1/40 • Number of events 34 • 2 years All registered patients that were evaluated are included.