Trial Outcomes & Findings for MLN9708 (Ixazomib) in Combination With Panobinostat and Dexamethasone in Multiple Myeloma (NCT NCT02057640)
NCT ID: NCT02057640
Last Updated: 2019-12-11
Results Overview
Number of Participants with Dose Limiting Toxicity of MLN9708 (lxazomib) according to CTCAE version 4.03
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
16 participants
Primary outcome timeframe
at 28 days from start of treatment
Results posted on
2019-12-11
Participant Flow
Participant milestones
| Measure |
DL1 - 3mg Lxazomib
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
|---|---|---|
|
Weeks 1-4
STARTED
|
4
|
3
|
|
Weeks 1-4
COMPLETED
|
4
|
3
|
|
Weeks 1-4
NOT COMPLETED
|
0
|
0
|
|
Phase II Portion of Study at DL2
STARTED
|
0
|
9
|
|
Phase II Portion of Study at DL2
COMPLETED
|
0
|
9
|
|
Phase II Portion of Study at DL2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
MLN9708 (Ixazomib) in Combination With Panobinostat and Dexamethasone in Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Phase I
n=4 Participants
Ixazomib - DL 1
|
Phase I/II
n=12 Participants
Ixazomib -DL2
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: at 28 days from start of treatmentPopulation: All participants who received treatment in the phase I portion of the study
Number of Participants with Dose Limiting Toxicity of MLN9708 (lxazomib) according to CTCAE version 4.03
Outcome measures
| Measure |
Dose Levels 1
n=4 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
|---|---|---|
|
Number of Participants With Dose Limiting Toxicity According to CTCAE Version 4.03
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: 4 months (102 days)Response to intervention as measured by international uniform response criteria and clinical benefit response according to modified EBMT response criteria, comparing myeloma panels obtained at the beginning of each cycle that include SPEP, 24 h UPEP, serum and urine IFEs, and serum free light chains to results at screening. In addition a baseline bone marrow exam and skeletal survey will be obtained and repeated as clinically indicated and for assessment of complete remission (bone marrow)
Outcome measures
| Measure |
Dose Levels 1
n=4 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
n=12 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
|---|---|---|
|
Response to Combination Therapy (Panobinostat, Dexamethasone, MLN9708)
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 1 year from start of treatmentProgression-free survival will be the number of days from study entry to progression or death of any cause, whichever comes first. Progression-free survival is survival with absence of progressive disease, defined by * An increase of 25% from lowest response value in any one or more of the following: * Serum M-component (absolute increase must be \>0.5 g/100 ml) \* * Urine M-component (absolute increase must be \>200mg per 24 h) * Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be \>100 mg/l) * Bone marrow plasma cell percentage (absolute % must be \>10%) * And / or: * Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas * Development of hypercalcemia (corrected serum calcium \>11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder
Outcome measures
| Measure |
Dose Levels 1
n=4 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
n=12 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
|---|---|---|
|
Progression-free Survival
|
1.2 months
Interval 0.7 to 6.0
|
3.5 months
Interval 0.9 to 7.4
|
SECONDARY outcome
Timeframe: up to 3 years from start of treatmentOverall survival for all will be the number of months from study entry to death from any cause.
Outcome measures
| Measure |
Dose Levels 1
n=4 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
n=12 Participants
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
|---|---|---|
|
Overall Survival
|
12.8 months
Interval 1.7 to 30.4
|
17.6 months
Interval 11.9 to 22.9
|
Adverse Events
DL1 - 3mg Lxazomib
Serious events: 1 serious events
Other events: 4 other events
Deaths: 4 deaths
DL2 - 4mg Lxazomib
Serious events: 5 serious events
Other events: 12 other events
Deaths: 9 deaths
Serious adverse events
| Measure |
DL1 - 3mg Lxazomib
n=4 participants at risk
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
n=12 participants at risk
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 4mg on day 1, 8, 15, 28
|
|---|---|---|
|
Infections and infestations
Hyperviscosity
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Infections and infestations
Lung Infection
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Skin and subcutaneous tissue disorders
Skin Infection
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Renal and urinary disorders
Urinary retention
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
Other adverse events
| Measure |
DL1 - 3mg Lxazomib
n=4 participants at risk
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
|
DL2 - 4mg Lxazomib
n=12 participants at risk
Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 4mg on day 1, 8, 15, 28
|
|---|---|---|
|
Blood and lymphatic system disorders
anemia
|
25.0%
1/4 • 30 days post last study drug administration
|
33.3%
4/12 • 30 days post last study drug administration
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
0.00%
0/4 • 30 days post last study drug administration
|
33.3%
4/12 • 30 days post last study drug administration
|
|
Blood and lymphatic system disorders
Lymphocyte count increased
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
0.00%
0/4 • 30 days post last study drug administration
|
25.0%
3/12 • 30 days post last study drug administration
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
25.0%
1/4 • 30 days post last study drug administration
|
33.3%
4/12 • 30 days post last study drug administration
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
0.00%
0/4 • 30 days post last study drug administration
|
25.0%
3/12 • 30 days post last study drug administration
|
|
Investigations
creatinine increased
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Nervous system disorders
dizziness
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
anorexia
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
General disorders
fever
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
General disorders
edema face
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.0%
1/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Skin and subcutaneous tissue disorders
scalp psoriasis
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Skin and subcutaneous tissue disorders
bruising
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Infections and infestations
respiratory infection
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Nervous system disorders
headache
|
25.0%
1/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
General disorders
fatigue
|
0.00%
0/4 • 30 days post last study drug administration
|
25.0%
3/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
constipation
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
General disorders
irritability
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Eye disorders
blurred vision
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Nervous system disorders
tremors
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
abdominal pain
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
dyspepsia
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
flatulence
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/4 • 30 days post last study drug administration
|
25.0%
3/12 • 30 days post last study drug administration
|
|
Psychiatric disorders
Depression
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
Hypalbuminemia
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Metabolism and nutrition disorders
Hypohosphatemia
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Renal and urinary disorders
Hemoglobinuria
|
0.00%
0/4 • 30 days post last study drug administration
|
16.7%
2/12 • 30 days post last study drug administration
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Infections and infestations
Breast infection
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Infections and infestations
Bronchial infection
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/4 • 30 days post last study drug administration
|
33.3%
4/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
1/4 • 30 days post last study drug administration
|
41.7%
5/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4 • 30 days post last study drug administration
|
50.0%
6/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
Taste changes
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
General disorders
Edema Limbs
|
25.0%
1/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
General disorders
Pain
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Nervous system disorders
Cognitive disturbance
|
25.0%
1/4 • 30 days post last study drug administration
|
0.00%
0/12 • 30 days post last study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Infections and infestations
Shingles
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
|
Gastrointestinal disorders
Belching
|
0.00%
0/4 • 30 days post last study drug administration
|
8.3%
1/12 • 30 days post last study drug administration
|
Additional Information
Jason Valent, MD
Cleveland Clinic Taussig Cancer Center
Phone: 216-445-7238
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place