Trial Outcomes & Findings for Aurora A Kinase Inhibitor MLN8237 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma (NCT NCT01034553)
NCT ID: NCT01034553
Last Updated: 2016-05-25
Results Overview
Patients were evaluated over the first cycle of treatment for Dose Limiting Toxicities. For this trail DLTs are as follows: An AE attributed (definitely, probably, or possibly) to study treatment during cycle 1 and the following criteria: Grade 4 Neutropenia Grade 4 Thrombocytopenia, or grade 3 with bleeding Febrile neutropenia Creatinine serum great than 2 times baseline or upper limit of normal Grade 3 or higher Fatigue Grade 3 or higher nausea, vomiting, or diarrhea Any grade 3 or higher Non-hematologic toxicity per NCI CTCAE V4.0 Inability to initiate the scheduled cycle 2, day 1 due to toxicity The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
26 participants
Primary outcome timeframe
28 days
Results posted on
2016-05-25
Participant Flow
Participant milestones
| Measure |
Phase I, Dose 0**
Patients receive 25mg aurora A kinase inhibitor MLN8237 once daily on days 1-14 and 1.3mg Bortezomib on days 1, 4,8, and 11.
Aurora A kinase inhibitor MLN8237: Given orally bortezomib: Given IV
|
Phase I, Dose 0
Patients receive 20mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
Aurora A kinase inhibitor MLN8237: Given orally bortezomib: Given IV
|
Phase I, Dose 1
Patients receive 30mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
Aurora A kinase inhibitor MLN8237: Given orally bortezomib: Given IV
|
Phase I, Dose 2
Patients receive 40mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
Aurora A kinase inhibitor MLN8237: Given orally bortezomib: Given IV
|
Phase I, Dose 3
Patients receive 50mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
Aurora A kinase inhibitor MLN8237: Given orally bortezomib: Given IV
|
Phase II, Dose 3
Patients receive 50mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
3
|
3
|
6
|
7
|
|
Overall Study
COMPLETED
|
3
|
4
|
3
|
3
|
6
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Aurora A Kinase Inhibitor MLN8237 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Baseline characteristics by cohort
| Measure |
All Patients
n=26 Participants
All Patients that received oral aurora A kinase inhibitor MLN8237 and bortezomib IV are summarized in this section.
Aurora A kinase inhibitor MLN8237: Given orally
|
|---|---|
|
Age, Continuous
|
64.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=5 Participants
|
|
Previous treatment
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 daysPatients were evaluated over the first cycle of treatment for Dose Limiting Toxicities. For this trail DLTs are as follows: An AE attributed (definitely, probably, or possibly) to study treatment during cycle 1 and the following criteria: Grade 4 Neutropenia Grade 4 Thrombocytopenia, or grade 3 with bleeding Febrile neutropenia Creatinine serum great than 2 times baseline or upper limit of normal Grade 3 or higher Fatigue Grade 3 or higher nausea, vomiting, or diarrhea Any grade 3 or higher Non-hematologic toxicity per NCI CTCAE V4.0 Inability to initiate the scheduled cycle 2, day 1 due to toxicity The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose.
Outcome measures
| Measure |
Dose 0**
n=3 Participants
Patients receive 25mg aurora A kinase inhibitor MLN8237 once daily on days 1-14 and 1.3mg Bortezomib on days 1, 4,8, and 11.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 0
n=4 Participants
Patients receive 20mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 1
n=3 Participants
Patients receive 30mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 2
n=3 Participants
Patients receive 40mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 3
n=6 Participants
Patients receive 50mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
|---|---|---|---|---|---|
|
Dose-limiting Toxicity (DLT) (Phase I)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Every 28 day cycle(up to 10 cycles)Population: All patients that received treatment were evaluated.
sCR: Normal serum FLC ratio, and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence, negative immunofixation of the serum and urine, \<5% plasma cells in bone marrow, disappearance of any soft tissue plasmacytomas, and normalization of FLC ratio. VGPR:PR and serum and urine M-component detectable by immunofixation but not on electrophoresis, or if serum measurable,≥90% or greater reduction in serum M-component plus urine M-component \<100 mg per 24h and if only measurable non-bone marrow parameter was FLC,≥90% or greater reduction in difference from involved and uninvolved FLC levels. PR:≥50% reduction of serum M-protein or reduction in 24-h urinary M-protein by ≥90% or to \<200 mg per 24h or if FLC, ≥50% decrease in the difference between involved and uninvolved FLC levels or ≥50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline percentage was ≥30%, and ≥50% reduction in the size of soft tissue plasmacytomas
Outcome measures
| Measure |
Dose 0**
n=7 Participants
Patients receive 25mg aurora A kinase inhibitor MLN8237 once daily on days 1-14 and 1.3mg Bortezomib on days 1, 4,8, and 11.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 0
n=3 Participants
Patients receive 20mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 1
n=3 Participants
Patients receive 30mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 2
n=13 Participants
Patients receive 40mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 3
Patients receive 50mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
|---|---|---|---|---|---|
|
Overall Response Rate to the Combination of MLN8237 and Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma.
Strong Complete Response
|
14.3 percentage of patients per dose level
|
0 percentage of patients per dose level
|
0 percentage of patients per dose level
|
0 percentage of patients per dose level
|
—
|
|
Overall Response Rate to the Combination of MLN8237 and Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma.
Very Good Partial Response
|
0 percentage of patients per dose level
|
33.3 percentage of patients per dose level
|
0 percentage of patients per dose level
|
7.7 percentage of patients per dose level
|
—
|
|
Overall Response Rate to the Combination of MLN8237 and Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma.
Partial Response
|
14.3 percentage of patients per dose level
|
0 percentage of patients per dose level
|
0 percentage of patients per dose level
|
23.1 percentage of patients per dose level
|
—
|
SECONDARY outcome
Timeframe: Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 yearsPopulation: All patients that received treatment were evaluated.
Outcome measures
| Measure |
Dose 0**
n=26 Participants
Patients receive 25mg aurora A kinase inhibitor MLN8237 once daily on days 1-14 and 1.3mg Bortezomib on days 1, 4,8, and 11.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 0
Patients receive 20mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 1
Patients receive 30mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 2
Patients receive 40mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 3
Patients receive 50mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
|---|---|---|---|---|---|
|
Progression-free Survival
|
5.9 Months
Interval 4.1 to 15.8
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 yearsPopulation: All patients that received treatment were evaluated.
Outcome measures
| Measure |
Dose 0**
n=26 Participants
Patients receive 25mg aurora A kinase inhibitor MLN8237 once daily on days 1-14 and 1.3mg Bortezomib on days 1, 4,8, and 11.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 0
Patients receive 20mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 1
Patients receive 30mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 2
Patients receive 40mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
Dose 3
Patients receive 50mg aurora A kinase inhibitor MLN8237 twice daily on days 1-7 and 1.5mg Bortezomib on days 1, 8,15, and 22.
\>
\> Aurora A kinase inhibitor MLN8237: Given orally
\>
\> bortezomib: Given IV
|
|---|---|---|---|---|---|
|
Overall Survival
|
23.6 Months
Interval 17.4 to
Insufficient number of participants with events
|
—
|
—
|
—
|
—
|
Adverse Events
All Patients
Serious events: 11 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Patients
n=26 participants at risk
bortezomib: Given IV
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
7.7%
2/26 • Number of events 2
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.8%
1/26 • Number of events 1
|
|
Cardiac disorders
Heart failure
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Ileus
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
3.8%
1/26 • Number of events 2
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Fatigue
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Pain
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Infections and infestations - Other, specify
|
11.5%
3/26 • Number of events 5
|
|
Infections and infestations
Urinary tract infection
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Lymphocyte count decreased
|
11.5%
3/26 • Number of events 4
|
|
Investigations
Neutrophil count decreased
|
19.2%
5/26 • Number of events 11
|
|
Investigations
Platelet count decreased
|
7.7%
2/26 • Number of events 7
|
|
Investigations
White blood cell decreased
|
11.5%
3/26 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
11.5%
3/26 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
7.7%
2/26 • Number of events 2
|
|
Nervous system disorders
Somnolence
|
3.8%
1/26 • Number of events 1
|
|
Psychiatric disorders
Psychiatric disorders - Other, specify
|
3.8%
1/26 • Number of events 1
|
Other adverse events
| Measure |
All Patients
n=26 participants at risk
bortezomib: Given IV
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
38.5%
10/26 • Number of events 24
|
|
Gastrointestinal disorders
Abdominal pain
|
3.8%
1/26 • Number of events 2
|
|
Gastrointestinal disorders
Bloating
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
61.5%
16/26 • Number of events 52
|
|
Gastrointestinal disorders
Dysphagia
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
19.2%
5/26 • Number of events 7
|
|
Gastrointestinal disorders
Nausea
|
69.2%
18/26 • Number of events 79
|
|
Gastrointestinal disorders
Vomiting
|
34.6%
9/26 • Number of events 14
|
|
General disorders
Edema limbs
|
3.8%
1/26 • Number of events 9
|
|
General disorders
Fatigue
|
80.8%
21/26 • Number of events 93
|
|
General disorders
Fever
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Gait disturbance
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Device related infection
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Infections and infestations - Other, specify
|
42.3%
11/26 • Number of events 29
|
|
Infections and infestations
Lung infection
|
7.7%
2/26 • Number of events 2
|
|
Infections and infestations
Sepsis
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
3.8%
1/26 • Number of events 1
|
|
Injury, poisoning and procedural complications
Bruising
|
3.8%
1/26 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fracture
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Alkaline phosphatase increased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
19.2%
5/26 • Number of events 36
|
|
Investigations
Creatinine increased
|
26.9%
7/26 • Number of events 15
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
3.8%
1/26 • Number of events 1
|
|
Investigations
INR increased
|
3.8%
1/26 • Number of events 5
|
|
Investigations
Lymphocyte count decreased
|
30.8%
8/26 • Number of events 33
|
|
Investigations
Neutrophil count decreased
|
46.2%
12/26 • Number of events 61
|
|
Investigations
Platelet count decreased
|
84.6%
22/26 • Number of events 128
|
|
Investigations
Weight loss
|
11.5%
3/26 • Number of events 3
|
|
Investigations
White blood cell decreased
|
26.9%
7/26 • Number of events 35
|
|
Metabolism and nutrition disorders
Anorexia
|
7.7%
2/26 • Number of events 3
|
|
Metabolism and nutrition disorders
Dehydration
|
3.8%
1/26 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
3.8%
1/26 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.8%
1/26 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
3.8%
1/26 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
7.7%
2/26 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
1/26 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.7%
2/26 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
3.8%
1/26 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
1/26 • Number of events 3
|
|
Nervous system disorders
Depressed level of consciousness
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
11.5%
3/26 • Number of events 3
|
|
Nervous system disorders
Peripheral motor neuropathy
|
26.9%
7/26 • Number of events 46
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
65.4%
17/26 • Number of events 111
|
|
Nervous system disorders
Somnolence
|
3.8%
1/26 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
3.8%
1/26 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
2/26 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
3.8%
1/26 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
26.9%
7/26 • Number of events 24
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.8%
1/26 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
3.8%
1/26 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
19.2%
5/26 • Number of events 7
|
|
Vascular disorders
Hypertension
|
3.8%
1/26 • Number of events 1
|
|
Vascular disorders
Phlebitis
|
3.8%
1/26 • Number of events 1
|
|
Vascular disorders
Thromboembolic event
|
3.8%
1/26 • Number of events 1
|
|
Vascular disorders
Vasculitis
|
3.8%
1/26 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place