Trial Outcomes & Findings for Ixazomib and Pevonedistat in Treating Patients With Multiple Myeloma That Has Come Back or Does Not Respond to Treatment (NCT NCT03770260)
NCT ID: NCT03770260
Last Updated: 2025-06-19
Results Overview
Number of participants experiencing a dose limiting toxicity to determine the maximum tolerated dose (MTD)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
8 participants
Primary outcome timeframe
At Day 28
Results posted on
2025-06-19
Participant Flow
Participant milestones
| Measure |
Dose Level 1
Pevonedistat 20 mg/meter squared given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 2
Pevonedistat 40 mg/meter squared given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 3
Pevonedistat 60 mg/meter squared given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Expansion
Pevonedistat at the maximum tolerated dose determined in the dose levels given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
1
|
0
|
|
Overall Study
COMPLETED
|
3
|
3
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Dose Level 1
Pevonedistat 20 mg/meter squared given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 2
Pevonedistat 40 mg/meter squared given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 3
Pevonedistat 60 mg/meter squared given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Expansion
Pevonedistat at the maximum tolerated dose determined in the dose levels given by infusion and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
|---|---|---|---|---|
|
Overall Study
Disease progression
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Ixazomib and Pevonedistat in Treating Patients With Multiple Myeloma That Has Come Back or Does Not Respond to Treatment
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=3 Participants
Pevonedistat 20 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 2
n=4 Participants
Pevonedistat 40 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 3
n=1 Participants
Pevonedistat 60 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=93 Participants
|
4 participants
n=4 Participants
|
1 participants
n=27 Participants
|
8 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: At Day 28Number of participants experiencing a dose limiting toxicity to determine the maximum tolerated dose (MTD)
Outcome measures
| Measure |
Dose Level 1
n=3 Participants
Patients receive pevonedistat 20 mg/meter squared by infusion and ixazomib citrate 4 mg by mouth on days 1, 8, and 15 of each 28-day cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Dose Level 2
n=4 Participants
Patients receive pevonedistat 40 mg/meter squared by infusion and ixazomib citrate 4 mg by mouth on days 1, 8, and 15 of each 28-day cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Dose Level 3
n=1 Participants
Patients receive pevonedistat 20 mg/meter squared by infusion and ixazomib citrate 4 mg by mouth on days 1, 8, and 15 of each 28-day cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|---|
|
Number of Participants Experiencing a Dose Limiting Toxicity (Dose Escalation)
Experienced a Dose Limiting Toxicity
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing a Dose Limiting Toxicity (Dose Escalation)
Did Not Experience a Dose Limiting Toxicity
|
3 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants Experiencing a Dose Limiting Toxicity (Dose Escalation)
Withdrew from Treatment
|
0 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 2 years after TreatmentPopulation: Did not complete dose escalation phase to enroll to the dose expansion phase.
Number of participants who experienced a grade 3-5 adverse event in the dose expansion group
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 2 Years after TreatmentPopulation: The dose escalation phase was not completed in order to enroll to the dose expansion phase
To determine the overall responses in patients receiving pevonedistat and ixazomib
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 3 monthsPopulation: This data was not collected.
To understand the concentration-effect relationship of both agents when taken together
Outcome measures
Outcome data not reported
Adverse Events
Dose Level 1
Serious events: 1 serious events
Other events: 3 other events
Deaths: 1 deaths
Dose Level 2
Serious events: 0 serious events
Other events: 4 other events
Deaths: 2 deaths
Dose Level 3
Serious events: 0 serious events
Other events: 1 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Dose Level 1
n=3 participants at risk
Pevonedistat 20 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 2
n=4 participants at risk
Pevonedistat 40 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 3
n=1 participants at risk
Pevonedistat 60 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
|---|---|---|---|
|
General disorders
Non-cardiac Chest Pain
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Vascular disorders
Pulmonary embolism
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
Other adverse events
| Measure |
Dose Level 1
n=3 participants at risk
Pevonedistat 20 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 2
n=4 participants at risk
Pevonedistat 40 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
Dose Level 3
n=1 participants at risk
Pevonedistat 60 mg/m\^2 given by a vein in the arm and ixazomib 4 mg taken by mouth on days 1, 8 and 15 of every 28-day cycle.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
1/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Blood and lymphatic system disorders
BUN elevated
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3 • Up to 2 years and 2 months
|
50.0%
2/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3 • Up to 2 years and 2 months
|
75.0%
3/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
General disorders
Fatigue
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
General disorders
Fever
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Infections and infestations
Upper respiratory infection
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Investigations
Lymphocyte count decreased
|
33.3%
1/3 • Up to 2 years and 2 months
|
100.0%
4/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Investigations
Platelet count decreased
|
33.3%
1/3 • Up to 2 years and 2 months
|
50.0%
2/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Investigations
Weight loss
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Investigations
White blood cell decreased
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
66.7%
2/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Musculoskeletal and connective tissue disorders
carpel tunnel repair
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Musculoskeletal and connective tissue disorders
Lower Leg Cramping
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Musculoskeletal and connective tissue disorders
Pain
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Alteration in Breathing Pattern
|
0.00%
0/3 • Up to 2 years and 2 months
|
25.0%
1/4 • Up to 2 years and 2 months
|
0.00%
0/1 • Up to 2 years and 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Skin and subcutaneous tissue disorders
Blisters
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
|
Vascular disorders
Hot flashes
|
0.00%
0/3 • Up to 2 years and 2 months
|
0.00%
0/4 • Up to 2 years and 2 months
|
100.0%
1/1 • Up to 2 years and 2 months
|
Additional Information
Grants Administrative Manager
Johns Hopkins University/SKCCC
Phone: 4439273568
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60