Ixazomib Citrate, Lenalidomide, Dexamethasone, and Daratu... | NCT03012880

ID	Type	Description
NCI-2017-00007	Registry Identifier	CTRP (Clinical Trial Reporting Program)
MC1686	Other Identifier	Mayo Clinic
16-006835	Other Identifier	Mayo Clinic Institutional Review Board

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the complete response rate (CR) of the four-drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic multiple myeloma (MM).

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR), and very good partial response (VGPR) rate with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab, when used as initial therapy in patients with previously untreated symptomatic MM.

II. To determine the progression free survival and overall survival among patients with previously untreated symptomatic MM following treatment with the four drug combination of Ixazomib, lenalidomide, dexamethasone and daratumumab followed by ixazomib and daratumumab maintenance till progression.

II. To determine the toxicities associated with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic MM.

TERTIARY OBJECTIVES:

I. To examine the proportion of minimal residual disease (MRD) negativity following induction therapy with the four-drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab.

II. To assess the quality of life using patient completed Functional Assessment of Cancer Treatment (FACT)/Gynecologic Oncology Group (GOG) questionnaires.

OUTLINE:

INDUCTION PHASE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab intravenously (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.

After completion of study treatment, patients are followed up every 3 or 6 months.

Label	Type	Description	Intervention Names
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)	Experimental	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.	Biological: Daratumumab Drug: Dexamethasone Drug: Ixazomib Citrate Other: Laboratory Biomarker Analysis Drug: Lenalidomide Other: Questionnaire Administration

Name	Type	Description	Arm Group Labels	Other Names
Daratumumab	Biological	Given IV	Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)

Measure	Description	Time Frame
Proportion of Patients Who Achieve a Confirmed Complete Response (CR)		2 years

Measure	Description	Time Frame
Proportion of Patients That Experienced a Grade 3 or Higher Adverse Event.	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.	2 years

Measure	Description	Time Frame
Minor Response Development (MRD)	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.	Up to 2 years

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min
Absolute neutrophil count (ANC) >= 1500/mm^3
Untransfused platelet count >= 75000/mm^3
Hemoglobin >= 8.0 g/dL
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
Measurable disease of multiple myeloma as defined by at least ONE of the following:
- Serum monoclonal protein >= 1.0 g/dL
- >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Previously untreated for myeloma or have received no more than one cycle of any treatment regimen; NOTE: Prior radiation therapy for the treatment of solitary plasmacytoma is permitted; prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
Provide informed written consent
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
Willing to follow strict birth control measures
- Female patients: if they are of childbearing potential, agree to one of the following:
  - Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND must also adhere to the guidelines of any treatment specific pregnancy prevention program, if applicable, OR
  - Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Male patients: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
  - Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
  - Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  - Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Willing to follow the requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
Willing to provide bone marrow and blood samples for planned research

Exclusion Criteria:

Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
Diagnosed or treated for another malignancy =< 2 years prior to registration or previously diagnosed with another malignancy and have any evidence of residual disease; NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
Other concurrent chemotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
Peripheral neuropathy >= grade 2 on clinical examination or grade 1 with pain during the screening period
Major surgery =< 14 days prior to registration
Systemic treatment with strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) =< 14 days prior to registration
Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction =< 6 months; Note: Prior to entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant
Radiotherapy =< 14 days prior to registration; NOTE: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
Known human immunodeficiency virus (HIV) positive
Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure), or known sensitivity to mammalian-derived products
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib, lenalidomide or dexamethasone including difficulty swallowing
Diarrhea > grade 1, based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading, in the absence of antidiarrheals

Name	Affiliation	Role
Shaji Kumar, M.D.	Mayo Clinic	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic		Rochester	Minnesota	55905	United States

Label	URL
Mayo Clinic Clinical Trials	View source

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 26, 2020

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00038 BG00140 BG00278

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Patients Who Achieve a Confirmed Complete Response (CR)

Posted

Number

95% Confidence Interval

proportion of participants

2 years

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00038 OG00140

Title

Denominators

Categories

Title	Measurements
	OG0000.32(0.184 to 0.474) OG0010.30(0.175 to 0.475)

Secondary

Proportion of Patients That Experienced a Grade 3 or Higher Adverse Event.

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.

Posted

Number

proportion of participants

2 years

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Overall Response Rate (ORR)

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.

Posted

Number

95% Confidence Interval

proportion of participants

2 years

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Overall Survival (OS)

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

Posted

Median

95% Confidence Interval

Months

2 years

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Progression Free Survival

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

Posted

Median

95% Confidence Interval

Months

2 years

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Rate of >= Very Good Partial Response (VGPR)

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.

Posted

Number

95% Confidence Interval

proportion of participants

2 years

ID	Title	Description
OG000	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.
OG001	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.

Other Pre-specified

Minor Response Development (MRD)

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.

Not Posted

Up to 2 years

Participants

Other Pre-specified

Neurotoxicity

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.

Not Posted

Baseline up to 2 years

Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected40 at risk
Glaucoma	Eye disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Ileus	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected40 at risk
Fever	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Flu like symptoms	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Multi-organ failure	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Appendicitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Infections and infestations - Oth spec	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected40 at risk
Lung infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0013 events2 affected40 at risk
Sepsis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0003 events3 affected39 at risk EG0010 events0 affected40 at risk
Creatinine increased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Urine output decreased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected40 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected40 at risk
Somnolence	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Syncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected39 at risk EG0010 events0 affected40 at risk
Confusion	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected39 at risk EG0011 events1 affected40 at risk
Hypotension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Thromboembolic event	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0009 events4 affected39 at risk EG00125 events8 affected40 at risk
Lymph node pain	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Blurred vision	Eye disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected40 at risk
Cataract	Eye disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected39 at risk EG0010 events0 affected40 at risk
Eye disorders - Other, specify	Eye disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected39 at risk EG0011 events1 affected40 at risk
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected39 at risk EG00121 events6 affected40 at risk
Dental caries	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG000212 events24 affected39 at risk EG001230 events24 affected40 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Gastrointestinal disorders - Oth spec	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected39 at risk EG0010 events0 affected40 at risk
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG000122 events24 affected39 at risk EG001167 events21 affected40 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00033 events14 affected39 at risk EG00153 events13 affected40 at risk
Edema limbs	General disorders	MedDRA 12	Systematic Assessment	EG0005 events3 affected39 at risk EG0014 events1 affected40 at risk
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG000614 events39 affected39 at risk EG001499 events38 affected40 at risk
Pain	General disorders	MedDRA 12	Systematic Assessment	EG0006 events2 affected39 at risk EG0013 events2 affected40 at risk
Infections and infestations - Oth spec	Infections and infestations	MedDRA 12	Systematic Assessment	EG00013 events4 affected39 at risk EG0011 events1 affected40 at risk
Lung infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0013 events2 affected40 at risk
Mucosal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Sepsis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Sinusitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG00011 events2 affected39 at risk EG0015 events4 affected40 at risk
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG00017 events9 affected39 at risk EG00121 events15 affected40 at risk
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG00010 events8 affected39 at risk EG0011 events1 affected40 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0004 events2 affected39 at risk EG0010 events0 affected40 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0008 events8 affected39 at risk EG00110 events10 affected40 at risk
CD4 lymphocytes decreased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Creatinine increased	Investigations	MedDRA 12	Systematic Assessment	EG00060 events8 affected39 at risk EG001113 events15 affected40 at risk
Lymphocyte count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000265 events22 affected39 at risk EG001282 events27 affected40 at risk
Lymphocyte count increased	Investigations	MedDRA 12	Systematic Assessment	EG0005 events4 affected39 at risk EG0011 events1 affected40 at risk
Neutrophil count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000122 events31 affected39 at risk EG00181 events22 affected40 at risk
Platelet count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000149 events23 affected39 at risk EG001112 events22 affected40 at risk
White blood cell decreased	Investigations	MedDRA 12	Systematic Assessment	EG00015 events6 affected39 at risk EG00150 events15 affected40 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected39 at risk EG00118 events5 affected40 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected40 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected39 at risk EG0011 events1 affected40 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Musculoskeletal, conn tissue - Oth spec	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0008 events2 affected39 at risk EG00111 events3 affected40 at risk
Neoplasms benign, mal, uncpec - Oth spec	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0013 events2 affected40 at risk
Nervous system disorders - Oth spec	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0005 events1 affected39 at risk EG0010 events0 affected40 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00069 events11 affected39 at risk EG00160 events3 affected40 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG000406 events32 affected39 at risk EG001392 events28 affected40 at risk
Presyncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0013 events1 affected40 at risk
Tremor	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events1 affected40 at risk
Anxiety	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0012 events1 affected40 at risk
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00015 events7 affected39 at risk EG0011 events1 affected40 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0004 events2 affected39 at risk EG0010 events0 affected40 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected40 at risk
Resp, thoracic, mediastinal - Oth spec	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0012 events2 affected40 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00046 events19 affected39 at risk EG00171 events22 affected40 at risk
Skin and subcut tissue disord - Oth spec	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected40 at risk
Hypertension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected40 at risk
Lymphocele	Vascular disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected40 at risk
Thromboembolic event	Vascular disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected39 at risk EG00134 events1 affected40 at risk

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
C556306	daratumumab
D003907	Dexamethasone
D002123	Calcium Dobesilate
C059464	auricularum
C018038	dexamethasone acetate
C004180	dexamethasone 21-phosphate
C548400	ixazomib
D000077269	Lenalidomide

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated
D001557	Benzenesulfonates
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D001190	Arylsulfonates
D017739	Arylsulfonic Acids
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D010797	Phthalimides
D010795	Phthalic Acids
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D010881	Piperidones
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D054833	Isoindoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A	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.	4	39	10	39	39	39
EG001	Cohort B	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.	1	40	8	40	40	40