Trial Outcomes & Findings for Bevacizumab, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Stage II or III Multiple Myeloma (NCT NCT00410605)
NCT ID: NCT00410605
Last Updated: 2017-09-01
Results Overview
Patient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria). Responses were analyzed by descriptive statistics and summarized in tabular format (frequency tables). Furthermore, two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response were computed using the method proposed by Chang, which takes into account the multiplicity problem associated with the two-stage testing procedure. The objective response rate was estimated by using Whitehead's bias-adjustment approach.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
39 participants
Primary outcome timeframe
Up to 5 years
Results posted on
2017-09-01
Participant Flow
Participants were recruited from the University of Wisconsin (UW) Hospital and Clinics, the UW 1 South Park Clinic, and the Wisconsin Oncology Network (WON) clinics between November 2006 and March 2011.
No events between enrollment and group assignment. All subjects enrolled are immediately assigned to Arm 1, "Bevacizumab, Dexamethasone, and Lenalidomide."
Participant milestones
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Overall Study
STARTED
|
39
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
25
|
Reasons for withdrawal
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Overall Study
Adverse Event
|
12
|
|
Overall Study
Physician Decision
|
3
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Started Non-Protocol Therapy
|
3
|
|
Overall Study
Stopped treatmen to collect stem cells
|
1
|
|
Overall Study
Transferred to another Institution
|
1
|
Baseline Characteristics
Bevacizumab, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Stage II or III Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=39 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Age, Customized
40-49 years
|
2 participants
n=5 Participants
|
|
Age, Customized
50-59 years
|
4 participants
n=5 Participants
|
|
Age, Customized
60-69 years
|
15 participants
n=5 Participants
|
|
Age, Customized
70-79 years
|
15 participants
n=5 Participants
|
|
Age, Customized
80-89 years
|
3 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
39 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 5 yearsPatient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria). Responses were analyzed by descriptive statistics and summarized in tabular format (frequency tables). Furthermore, two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response were computed using the method proposed by Chang, which takes into account the multiplicity problem associated with the two-stage testing procedure. The objective response rate was estimated by using Whitehead's bias-adjustment approach.
Outcome measures
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=39 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bevacizumab and Lenalidomide
|
64 percentage of participants
Interval 48.0 to 77.0
|
PRIMARY outcome
Timeframe: up to five yearsPatient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria). Progression free survival was summarized using point estimates of the median time to progression and associated 95% confidence intervals. The data was presented graphically using Kaplan-Meier plots. Exploratory analysis, including multivariate Cox regression with demographic variables and markers of myeloma activity as covariates was performed.
Outcome measures
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=39 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Progression Free Survival (Time to Progression)
|
9 months
Interval 1.0 to 58.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsAdverse events/toxicities were collected during regular clinical visits. Confidence intervals for the estimate of the true number of patients suffereing from grade 3 or 4 toxicities per common terminology criteria were calculated using the Wilson interval. Ninety-five percent confidence intervals for the proportions of patients with complications (grade 3 or higher toxicities) were constructed.
Outcome measures
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=39 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Toxicity and Tolerability of the Bevacizumab and Lenalidomide Combination
|
72 percentage of participants
Interval 59.0 to 82.0
|
SECONDARY outcome
Timeframe: BaselineA Wilconxon signed-rank test conducted to determine if biomarker levels differed between baseline levels and those after three full cycles of treatment for all patients.
Outcome measures
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=34 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
IL-6 level range
|
17.2 mg per liter
Standard Deviation 65.1
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
MIP-1 level range
|
0.039 mg per liter
Standard Deviation 0.025
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
VEGF level range
|
0.084 mg per liter
Standard Deviation 0.066
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
VEGFR1 level range
|
0.12 mg per liter
Standard Deviation 0.11
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
VEGFR2 level range
|
8.85 mg per liter
Standard Deviation 2.08
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: Outcome measure data were not collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Course 4 Day 1 (3 Months Post-baseline)A Wilconxon signed-rank test conducted to determine if biomarker levels differed between baseline levels and those after three full cycles of treatment for all patients.
Outcome measures
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=34 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
IL-6 level range
|
5.5 mg per liter
Standard Deviation 3.4
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
MIP-1 level range
|
0.047 mg per liter
Standard Deviation 0.044
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
VEGF level range
|
0.054 mg per liter
Standard Deviation 0.042
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
VEGFR1 level range
|
0.12 mg per liter
Standard Deviation 0.088
|
|
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
VEGFR2 level range
|
8.17 mg per liter
Standard Deviation 2.29
|
Adverse Events
Bevacizumab, Dexamethasone, and Lenalidomide
Serious events: 22 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=39 participants at risk
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Cardiac disorders
Atrial fibrillation
|
7.7%
3/39
|
|
Cardiac disorders
Atrial flutter
|
2.6%
1/39
|
|
Cardiac disorders
Heart failure
|
2.6%
1/39
|
|
Cardiac disorders
Left Ventricular Systolic Dysfunction
|
2.6%
1/39
|
|
Endocrine disorders
Hypothyroidism
|
2.6%
1/39
|
|
Eye disorders
Retinal Detachment
|
2.6%
1/39
|
|
Gastrointestinal disorders
Abdominal Pain
|
5.1%
2/39
|
|
Gastrointestinal disorders
Colonic Perforation
|
2.6%
1/39
|
|
Gastrointestinal disorders
Diarrhea
|
2.6%
1/39
|
|
Gastrointestinal disorders
Dry Mouth
|
2.6%
1/39
|
|
Gastrointestinal disorders
Duodenal Hemorrhage
|
2.6%
1/39
|
|
Gastrointestinal disorders
Ileus
|
2.6%
1/39
|
|
Gastrointestinal disorders
Mucositis Oral
|
2.6%
1/39
|
|
Gastrointestinal disorders
Small Intestinal Perforation
|
5.1%
2/39
|
|
General disorders
Death NOS
|
5.1%
2/39
|
|
General disorders
Edema Limbs
|
5.1%
2/39
|
|
General disorders
Fever
|
2.6%
1/39
|
|
Infections and infestations
Infections and Infestations, Other
|
2.6%
1/39
|
|
Infections and infestations
Lung Infection
|
5.1%
2/39
|
|
Infections and infestations
Mucosal Infection
|
2.6%
1/39
|
|
Infections and infestations
Upper Respiratory Infection
|
2.6%
1/39
|
|
Investigations
Blood Bilirubin Increased
|
2.6%
1/39
|
|
Investigations
Cardiac Troponin T Increased
|
5.1%
2/39
|
|
Investigations
Lymphocyte Count Decreased
|
2.6%
1/39
|
|
Investigations
Neutrophil Count Decreased
|
5.1%
2/39
|
|
Investigations
White Blood Cell Decreased
|
2.6%
1/39
|
|
Metabolism and nutrition disorders
Anorexia
|
2.6%
1/39
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.6%
1/39
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.6%
1/39
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
2.6%
1/39
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.6%
1/39
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
2.6%
1/39
|
|
Musculoskeletal and connective tissue disorders
Chest Wall Pain
|
2.6%
1/39
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.6%
1/39
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
2.6%
1/39
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment Related Secondary Malignancy - Chronic Lymphocytic Leukemia
|
2.6%
1/39
|
|
Nervous system disorders
Dysgeusia
|
2.6%
1/39
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
5.1%
2/39
|
|
Psychiatric disorders
Confusion
|
2.6%
1/39
|
|
Psychiatric disorders
Depression
|
2.6%
1/39
|
|
Renal and urinary disorders
Acute Kidney Injury
|
7.7%
3/39
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.3%
4/39
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.6%
1/39
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.6%
1/39
|
|
Vascular disorders
Hypertension
|
2.6%
1/39
|
|
Vascular disorders
Thromboembolic Event
|
10.3%
4/39
|
Other adverse events
| Measure |
Bevacizumab, Dexamethasone, and Lenalidomide
n=39 participants at risk
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
bevacizumab: Given IV
lenalidomide: Given orally
dexamethasone: Given orally
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
7.7%
3/39
|
|
Investigations
Alanine aminotransferase increased
|
10.3%
4/39
|
|
Investigations
Alkaline Phosphatase Increased
|
10.3%
4/39
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
7.7%
3/39
|
|
Blood and lymphatic system disorders
Anemia
|
53.8%
21/39
|
|
Metabolism and nutrition disorders
Anorexia
|
35.9%
14/39
|
|
Psychiatric disorders
Anxiety
|
10.3%
4/39
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.3%
4/39
|
|
Investigations
Aspartate aminotransferase increased
|
5.1%
2/39
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.5%
8/39
|
|
Investigations
Blood bilirubin increased
|
7.7%
3/39
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
12.8%
5/39
|
|
Eye disorders
Blurred vision
|
12.8%
5/39
|
|
Injury, poisoning and procedural complications
Bruising
|
12.8%
5/39
|
|
General disorders
Chills
|
10.3%
4/39
|
|
Psychiatric disorders
Confusion
|
5.1%
2/39
|
|
Gastrointestinal disorders
Constipation
|
20.5%
8/39
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.5%
8/39
|
|
Investigations
Creatinine increased
|
15.4%
6/39
|
|
Psychiatric disorders
Depression
|
5.1%
2/39
|
|
Gastrointestinal disorders
Diarrhea
|
51.3%
20/39
|
|
Nervous system disorders
Dizziness
|
10.3%
4/39
|
|
Gastrointestinal disorders
Dry mouth
|
5.1%
2/39
|
|
Nervous system disorders
Dysgeusia
|
15.4%
6/39
|
|
Gastrointestinal disorders
Dyspepsia
|
10.3%
4/39
|
|
Gastrointestinal disorders
Dysphagia
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
38.5%
15/39
|
|
General disorders
Edema limbs
|
20.5%
8/39
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
30.8%
12/39
|
|
General disorders
Fatigue
|
66.7%
26/39
|
|
General disorders
Fever
|
10.3%
4/39
|
|
Gastrointestinal disorders
Flatulence
|
5.1%
2/39
|
|
Vascular disorders
Flushing
|
7.7%
3/39
|
|
Musculoskeletal and connective tissue disorders
generalized muscle weakness
|
10.3%
4/39
|
|
Infections and infestations
Gum infection
|
5.1%
2/39
|
|
Nervous system disorders
Headache
|
28.2%
11/39
|
|
Gastrointestinal disorders
Hemorrhoids
|
5.1%
2/39
|
|
Metabolism and nutrition disorders
hyperglycemia
|
51.3%
20/39
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
17.9%
7/39
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
20.5%
8/39
|
|
Vascular disorders
Hypertension
|
17.9%
7/39
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
35.9%
14/39
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
43.6%
17/39
|
|
Metabolism and nutrition disorders
Hypokalemia
|
12.8%
5/39
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.6%
10/39
|
|
Psychiatric disorders
Insomnia
|
23.1%
9/39
|
|
Investigations
Lymphocyte count decreased
|
38.5%
15/39
|
|
Infections and infestations
Mucosal infection
|
7.7%
3/39
|
|
Gastrointestinal disorders
Mucositis oral
|
41.0%
16/39
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
5.1%
2/39
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.3%
4/39
|
|
Gastrointestinal disorders
Nausea
|
25.6%
10/39
|
|
Investigations
Neutrophil count decreased
|
74.4%
29/39
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.8%
5/39
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
38.5%
15/39
|
|
Psychiatric disorders
Personality change
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
10.3%
4/39
|
|
Investigations
Platelet count decreased
|
69.2%
27/39
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.1%
2/39
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
25.6%
10/39
|
|
Respiratory, thoracic and mediastinal disorders
Sinus disorder
|
12.8%
5/39
|
|
Infections and infestations
Sinusitis
|
5.1%
2/39
|
|
Infections and infestations
Skin infection
|
5.1%
2/39
|
|
Infections and infestations
Tooth infection
|
5.1%
2/39
|
|
Nervous system disorders
Tremor
|
12.8%
5/39
|
|
Infections and infestations
Upper respiratory infection
|
20.5%
8/39
|
|
Renal and urinary disorders
Urinary frequency
|
5.1%
2/39
|
|
Infections and infestations
Urinary Tract Infection
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
20.5%
8/39
|
|
Gastrointestinal disorders
Vomiting
|
12.8%
5/39
|
|
Investigations
Weight loss
|
25.6%
10/39
|
|
Investigations
White blood cell decreased
|
66.7%
26/39
|
Additional Information
Dr. Natalie Callander
Univerisity of Wisconsin Carbone Cancer Center
Phone: 608-265-8690
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60