Trial Outcomes & Findings for Bortezomib, Lenalidomide and Dexamethasone Combination Therapy in Patients With Newly Diagnosed Multiple Myeloma (NCT NCT00378105)
NCT ID: NCT00378105
Last Updated: 2025-02-28
Results Overview
Overall Response (OR) was defined as partial response (PR) or better. Response was assessed according to European Group for Blood and Marrow Transplant criteria, modified to include nCR and VGPR, from the International Uniform Response Criteria.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE1/PHASE2
Target enrollment
68 participants
Primary outcome timeframe
Full response assessment was conducted at the end of cycle 8 (average of168 days) and after cycle 4 (84 days) for patients proceeding to transplant.
Results posted on
2025-02-28
Participant Flow
A total of 68 patients were enrolled in the United States. For the phase I part, this study enrolled 33 eligible patients between Sep13, 2006 and Aug16, 2007. For the phase II part, this study enrolled 35 eligible patients between Aug 20, 2007 and Feb18, 2008.
Participants were screened over a two-week period.
Participant milestones
| Measure |
Phase 2 Pupulation
Each subject received the maximum planned dose of 1.3 mg/m2/IV bortezomib daily Days 1, 4, 8 and 11 followed by a 10-day rest period, 20 mg PO dexamethasone single daily oral dose Days 1, 2, 4, 5, 8, 9, 11, 12 and25 mg/PO/QD (every day)lenalidomide daily Days 1-14 followed by 7-day rest every 21 days x 4 cycles and then at 10 mg/day on the same schedule for cycles 5 - 8. Each cycle of treatment consisted of 21 days.
|
Phase 1 Population
Four levels of dose were evaluated and a standard 3+3 dose escalation schema was used to determine the MTD and additional patients were evaluated on the MTD level.
1. Level 1 1 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 15 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
2. Level 2 1.3 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 15 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
3. Level 3 1.3 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 20 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
4. Level 4 1.3 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 25 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
31
|
|
Overall Study
COMPLETED
|
5
|
11
|
|
Overall Study
NOT COMPLETED
|
30
|
20
|
Reasons for withdrawal
| Measure |
Phase 2 Pupulation
Each subject received the maximum planned dose of 1.3 mg/m2/IV bortezomib daily Days 1, 4, 8 and 11 followed by a 10-day rest period, 20 mg PO dexamethasone single daily oral dose Days 1, 2, 4, 5, 8, 9, 11, 12 and25 mg/PO/QD (every day)lenalidomide daily Days 1-14 followed by 7-day rest every 21 days x 4 cycles and then at 10 mg/day on the same schedule for cycles 5 - 8. Each cycle of treatment consisted of 21 days.
|
Phase 1 Population
Four levels of dose were evaluated and a standard 3+3 dose escalation schema was used to determine the MTD and additional patients were evaluated on the MTD level.
1. Level 1 1 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 15 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
2. Level 2 1.3 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 15 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
3. Level 3 1.3 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 20 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
4. Level 4 1.3 mg/m2/IV bortezomib daily Days 1,4, 8 and 11 40 mg PO dexamethasone daily Days 1, 2, 4, 5, 8, 9, 11, 12 and 25 mg/PO/day lenalidomide daily Days 1-14 followed by 7-day rest every 21 days
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
3
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Going to transplant
|
8
|
7
|
|
Overall Study
Progressive disease
|
3
|
3
|
|
Overall Study
remain on study
|
11
|
3
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Going non-protocol therapy
|
1
|
0
|
|
Overall Study
necessity to increase lenalidomide dose
|
1
|
0
|
Baseline Characteristics
Bortezomib, Lenalidomide and Dexamethasone Combination Therapy in Patients With Newly Diagnosed Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Phase 1 Population
n=31 Participants
|
Phase 2 Population
n=35 Participants
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57 years
n=5 Participants
|
59 years
n=7 Participants
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Full response assessment was conducted at the end of cycle 8 (average of168 days) and after cycle 4 (84 days) for patients proceeding to transplant.Population: The numbers excluded 2 patients who went off study prior to start of therapy
Overall Response (OR) was defined as partial response (PR) or better. Response was assessed according to European Group for Blood and Marrow Transplant criteria, modified to include nCR and VGPR, from the International Uniform Response Criteria.
Outcome measures
| Measure |
Phase 1 Population
n=31 Participants
|
Phase II Population
n=35 Participants
|
Total
n=66 Participants
|
|---|---|---|---|
|
Objective Response Rate of the Drug Combination in This Patient Populations.
|
100 percentage of participants
Interval 91.0 to 100.0
|
100 percentage of participants
Interval 92.0 to 100.0
|
100 percentage of participants
Interval 96.0 to 100.0
|
SECONDARY outcome
Timeframe: PFS rate at 18 monthsPopulation: This numbers excluded 2 patients who went off study prior to start of therapy.
PD from European Bone Marrow Transplant (EBMT) Response Criteria Required one or more: \>25% increased in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, or \>25% increased in 24-hour urinary light chain excretion (must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation), or \>25% increased in plasma cells in a bone marrow aspirate or biopsy (must also be an absolute increase of at least 10%) Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas. Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture). Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL or 2.8 mmol/L not attributable to any other cause). PFS was measured from treatment initiation to progression or death, censored at the date patients were last known to be alive and disease free
Outcome measures
| Measure |
Phase 1 Population
n=66 Participants
|
Phase II Population
|
Total
|
|---|---|---|---|
|
Estimated 18-month Progression Free Survival (PFS) Rate
|
75 Percentage of participants
Interval 63.0 to 84.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Response rate at 18 monthsDuration of response was measured from first response to progression or death, censored at the date patients were last known to be alive and disease free for patients who had not progressed or died.
Outcome measures
| Measure |
Phase 1 Population
n=66 Participants
|
Phase II Population
|
Total
|
|---|---|---|---|
|
Percentage of Patients Who Remained in Response for More Than 18 Months
|
68 Percentage of participants
Interval 55.0 to 79.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Survival rate at 18 monthsOverall survival was measured from treatment initiation to death, censored at the date patients were last known to be alive for those who had not died.
Outcome measures
| Measure |
Phase 1 Population
n=66 Participants
|
Phase II Population
|
Total
|
|---|---|---|---|
|
Estimated 18-month Overall Survival Rate
|
97 Percentage of participants
Interval 88.0 to 99.0
|
—
|
—
|
Adverse Events
All Patients
Serious events: 37 serious events
Other events: 66 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Patients
n=66 participants at risk
|
|---|---|
|
Nervous system disorders
Sensory Neuropathy
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Fatigue
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
Musculoskeletal and connective tissue disorders
Muscle Pain
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Skin and subcutaneous tissue disorders
Rash/ desquamation
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
Neuropathic pain
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Extremity Pain
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Insomnia
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Dizziness
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
Motor Neuropathy
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Neutropenia
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
Anxiety
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
13.6%
9/66 • Safety was assessed every cycle during the therapy.
|
|
Eye disorders
Blurred Vision
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Elevated alanine transaminase
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
Altered Mental Status
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/ Upper Respiratory Event
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
Agitation
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Ear and labyrinth disorders
Altered Hearing
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Anemia
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Cardiac disorders
Altered QTc interval
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Elevated Creatinine
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.0%
2/66 • Safety was assessed every cycle during the therapy.
|
|
Infections and infestations
Infection
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Vascular disorders
Stomach Hemorrhage
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
|
Cardiac disorders
Atrial Fibrillation
|
1.5%
1/66 • Safety was assessed every cycle during the therapy.
|
Other adverse events
| Measure |
All Patients
n=66 participants at risk
|
|---|---|
|
Nervous system disorders
Sensory Neuropathy
|
78.8%
52/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Fatigue
|
60.6%
40/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
Constipation
|
60.6%
40/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Peripheral Edema
|
45.5%
30/66 • Safety was assessed every cycle during the therapy.
|
|
Musculoskeletal and connective tissue disorders
Muscle Pain
|
42.4%
28/66 • Safety was assessed every cycle during the therapy.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
34.8%
23/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
Diarrhea
|
34.8%
23/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
Nausea
|
31.8%
21/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
Neuropathic Pain
|
28.8%
19/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
Extremity pain
|
27.3%
18/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Insomnia
|
28.8%
19/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.8%
17/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Dizziness
|
22.7%
15/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Other Constitutional Event
|
18.2%
12/66 • Safety was assessed every cycle during the therapy.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
18.2%
12/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
Motor Neuropathy
|
16.7%
11/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Skin and subcutaneous tissue disorders
Pruritis/itching
|
18.2%
12/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
Anxiety
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Eye disorders
Blurred Vision
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Elevated Alanine Transaminase
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
Altered mental status
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.6%
5/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
7.6%
5/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/upper respiratory event
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
Agitation
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Ear and labyrinth disorders
Altered hearing
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Anemia
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.6%
9/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
bloating
|
13.6%
9/66 • Safety was assessed every cycle during the therapy.
|
|
Musculoskeletal and connective tissue disorders
joint pain
|
13.6%
9/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
anorexia
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
dysgeusia
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
tremor
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
cognitive disturbance
|
12.1%
8/66 • Safety was assessed every cycle during the therapy.
|
|
Infections and infestations
infection
|
15.2%
10/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
metabolic lab disorder
|
19.7%
13/66 • Safety was assessed every cycle during the therapy.
|
|
Ear and labyrinth disorders
tinnitus
|
10.6%
7/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
dysarthria
|
10.6%
7/66 • Safety was assessed every cycle during the therapy.
|
|
Musculoskeletal and connective tissue disorders
bone pain
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Endocrine disorders
cushingoid appearance
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
depression
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Nervous system disorders
headache
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
hypocalcemia
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
Skin and subcutaneous tissue disorders
sweating
|
9.1%
6/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
head and neck edema
|
7.6%
5/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
Abdominal pain
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Investigations
Alkaline phosphatase increased
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Eye disorders
dry eye
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
Genital and trunk edema
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Vascular disorders
flushing
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Vascular disorders
hypotension
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
personality change
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
chills
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
vomiting
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Investigations
weight gain
|
6.1%
4/66 • Safety was assessed every cycle during the therapy.
|
|
Psychiatric disorders
confusion
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
General disorders
gait disturbance
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Gastrointestinal disorders
gastritis
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Musculoskeletal and connective tissue disorders
neck pain
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
|
Renal and urinary disorders
urinary frequency
|
4.5%
3/66 • Safety was assessed every cycle during the therapy.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60