Trial Outcomes & Findings for Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma (NCT NCT00920855)
NCT ID: NCT00920855
Last Updated: 2012-10-04
Results Overview
Maximum tolerated dose was the dose that was 1 step lower than the dose where at least one third of patients experienced DLT. A DLT was defined as any of the following occurring during the first cycle: * grade 4 hematologic toxicity without regard for relationship to study drug treatment * thrombocytopenia grade 3 with grade 3 or grade 4 hemorrhage * grade 3 febrile neutropenia * grade 3 or grade 4 nausea and vomiting refractory to anti emetic therapy * any study drug related grade 3 or grade 4 nonhematologic toxicity * any drug related death Toxicity grades (3=severe AE and 4=life-threatening or disabling AE) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
40 participants
Primary outcome timeframe
Day 1 - 28
Results posted on
2012-10-04
Participant Flow
Fifty-one patients were screened and forty from 10 U.S. centers were enrolled. Reasons for not enrolling were failed to meet inclusion and/or exclusion criteria (10) and an adverse event (1).
Participant milestones
| Measure |
Bendamustine 50 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
4
|
31
|
|
Overall Study
Safety and Efficacy Populations
|
5
|
4
|
31
|
|
Overall Study
COMPLETED
|
0
|
1
|
9
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
22
|
Reasons for withdrawal
| Measure |
Bendamustine 50 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
4
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
6
|
|
Overall Study
Disease progression
|
2
|
1
|
10
|
|
Overall Study
Noncompliance to study medication
|
0
|
0
|
1
|
|
Overall Study
Response plateau; started maintenance
|
0
|
0
|
1
|
Baseline Characteristics
Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
62.8 years
STANDARD_DEVIATION 18.17 • n=5 Participants
|
67.0 years
STANDARD_DEVIATION 9.49 • n=7 Participants
|
64.5 years
STANDARD_DEVIATION 10.68 • n=5 Participants
|
64.6 years
STANDARD_DEVIATION 11.38 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
24 participants
n=5 Participants
|
32 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
5 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
31 participants
n=5 Participants
|
40 participants
n=4 Participants
|
|
Body Surface Area (BSA)
|
1.76 m^2
STANDARD_DEVIATION 0.234 • n=5 Participants
|
1.81 m^2
STANDARD_DEVIATION 0.177 • n=7 Participants
|
1.90 m^2
STANDARD_DEVIATION 0.265 • n=5 Participants
|
1.87 m^2
STANDARD_DEVIATION 0.254 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 - 28Population: Safety population
Maximum tolerated dose was the dose that was 1 step lower than the dose where at least one third of patients experienced DLT. A DLT was defined as any of the following occurring during the first cycle: * grade 4 hematologic toxicity without regard for relationship to study drug treatment * thrombocytopenia grade 3 with grade 3 or grade 4 hemorrhage * grade 3 febrile neutropenia * grade 3 or grade 4 nausea and vomiting refractory to anti emetic therapy * any study drug related grade 3 or grade 4 nonhematologic toxicity * any drug related death Toxicity grades (3=severe AE and 4=life-threatening or disabling AE) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Participants With Dose Limiting Toxicity (DLT)
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Up to 7.5 months (eight 28-day cycles)Population: Efficacy population
Overall tumor response is the sum of a complete response (CR), very good partial response (VGPR), partial response (PR) and minimal response (MR). A modified version of the Bladé criteria for response was used. Abbreviated definitions for the response categories can be found in the description of outcome #3.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Percentage of Participants With An Overall Tumor Response As Assessed By the Investigator
|
40.0 percentage of participants
Interval 5.27 to 85.34
|
25.0 percentage of participants
Interval 0.63 to 80.59
|
51.6 percentage of participants
Interval 33.06 to 69.85
|
SECONDARY outcome
Timeframe: up to 7.5 months (eight 28-day cycles)Population: Efficacy population
Abbreviated criteria for response categories: CR includes the disappearance of the original monoclonal protein (M-protein) from blood and urine, and \<5% plasma cells in the bone marrow, and no increase in size/number of lytic bone lesions, and disappearance of soft tissue plasmacytomas for \>=4 weeks. VGPR includes serum and urine M-protein detectable by immunofixation but not electrophoresis, and reduction in 24-hr urinary light chain excretion by \<100 mg, and disappearance of soft tissue plasmacytomas for \>= 4 weeks, and no increase in size/number of lytic bone lesions. PR includes a \>=50% reduction in serum M-protein, and reduction in 24-hr urinary light chain excretion by either \>=90% or to \<200 mg, and \>=50% reduction in size of soft tissue plasmacytomas, and no increase in size/number of lytic bone lesions. MR includes a \>=25% and \<=49% reduction in serum M-protein. SD does not meet criteria for the other response categories. See outcome #4 for a definition of PD.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Participants' Best Tumor Response as Assessed by the Investigator
Complete response (CR)
|
0 participants
|
0 participants
|
1 participants
|
|
Participants' Best Tumor Response as Assessed by the Investigator
Very good partial response (VGPR)
|
0 participants
|
0 participants
|
2 participants
|
|
Participants' Best Tumor Response as Assessed by the Investigator
Partial response (PR)
|
1 participants
|
0 participants
|
8 participants
|
|
Participants' Best Tumor Response as Assessed by the Investigator
Minimal response (MR)
|
1 participants
|
1 participants
|
5 participants
|
|
Participants' Best Tumor Response as Assessed by the Investigator
Stable disease (SD)
|
2 participants
|
2 participants
|
13 participants
|
|
Participants' Best Tumor Response as Assessed by the Investigator
Progressive disease (PD)
|
1 participants
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: up to 8.6 monthsPopulation: Safety population
Time to progression was defined as the time from initiation of therapy to progressive disease (PD). PD requires at least one of the following: * \>25% increase in serum monoclonal paraprotein (which must also be an absolute increase of at least 5 g/L), * \>25% increase in 24-hour urinary light chain excretion (which must also be an absolute increase of at least 200 mg/24 h), * \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy (which must also be an absolute increase of at least 10%), * definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas, * the development of new bone lesions or soft tissue plasmacytomas, * the development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=40 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Kaplan-Meier Estimate for Time to Progression (TTP)
|
8.4 months
Interval 4.03 to
Upper boundary was not estimated due to the limited number of participants with events.
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 23 monthsPopulation: Safety population
Progression free survival is the time between the date of initiation of therapy to progressive disease (PD) or death from any cause, whichever occurs first. See outcome #4 for a definition of PD.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=40 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Kaplan-Meier Estimate for Progression-Free Survival
|
15.21 months
Interval 5.22 to 16.63
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 8.5 monthsPopulation: Participants who had a response
Time to first response is defined as the time from the initiation of therapy to the first evidence of a confirmed response (ie, CR, VGPR, PR, or MR).
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=19 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Time to the First Response
|
1.9 months
Standard Deviation 1.51
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 8.5 monthsPopulation: Participants who had a response
Duration of response (DR) is defined as the time from the first response to progressive disease (PD). See outcome #4 for a PD definition.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=19 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Kaplan-Meier Estimate for Duration of Response
|
NA months
Interval 6.55 to
Median and upper boundary were not estimated due to the limited number of participants with events.
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 23 monthsPopulation: Safety population
Overall survival is defined as the time from initiation of therapy to death from any cause or last follow-up visit.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=40 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Kaplan-Meier Estimate for Overall Survival (OS)
|
17.82 months
Interval 15.83 to
Upper boundary was not estimated due to the limited number of participants with events.
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 8.5 months. Deaths are reported up to 18 monthsPopulation: Safety population
Counts of participants who had AEs are summarized in a variety of categories. Severity and relatedness to study drug are in the opinion of the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0. Severity is rated on a 5-point scale: 1=mild, 2=moderate, 3=severe, 4=life threatening or disabling, and 5= death related to AE. Relatedness is assessed on a 5-point scale: not related, unlikely, possible, probable and definite. Definite, probable and possible answers are reported as 'related' to study medication. Deaths are reported up to 18 months. All the deaths occurred beyond the treatment-emergent timeframe since they occurred 6.5-16 months after the final dosing. All other parts of the summary represent the treatment-emergent timeframe (up to 8.5 months) which is the treatment period plus 30 days.
Outcome measures
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 Participants
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Summary of Participants With Adverse Events (AEs)
Any adverse event
|
5 participants
|
4 participants
|
31 participants
|
|
Summary of Participants With Adverse Events (AEs)
Any non-haematologic adverse event
|
5 participants
|
4 participants
|
31 participants
|
|
Summary of Participants With Adverse Events (AEs)
Severe adverse event (grade 3 or 4)
|
3 participants
|
3 participants
|
22 participants
|
|
Summary of Participants With Adverse Events (AEs)
Treatment-related adverse events
|
4 participants
|
4 participants
|
31 participants
|
|
Summary of Participants With Adverse Events (AEs)
Deaths
|
1 participants
|
0 participants
|
5 participants
|
|
Summary of Participants With Adverse Events (AEs)
Serious adverse events
|
0 participants
|
1 participants
|
7 participants
|
|
Summary of Participants With Adverse Events (AEs)
Withdrawn from study due to AE
|
2 participants
|
2 participants
|
5 participants
|
Adverse Events
Bendamustine 50 mg/m^2 Cohort
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Bendamustine 70 mg/m^2 Cohort
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Bendamustine 90 mg/m^2 Cohort
Serious events: 7 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 participants at risk
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 participants at risk
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 participants at risk
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
General disorders
Pyrexia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Infections and infestations
Cystitis
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Infections and infestations
Sepsis syndrome
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
Other adverse events
| Measure |
Bendamustine 50 mg/m^2 Cohort
n=5 participants at risk
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 50 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 70 mg/m^2 Cohort
n=4 participants at risk
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 70 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
Bendamustine 90 mg/m^2 Cohort
n=31 participants at risk
Bortezomib 1.0 mg/m\^2/dose (days 1, 4, 8 and 11) by intravenous push and Bendamustine 90 mg/m\^2/dose (days 1 and 4) intravenously for up to eight 28 day cycles.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
40.0%
2/5 • up to 8.5 months
|
75.0%
3/4 • up to 8.5 months
|
61.3%
19/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
32.3%
10/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/5 • up to 8.5 months
|
75.0%
3/4 • up to 8.5 months
|
48.4%
15/31 • up to 8.5 months
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Eye disorders
Eye irritation
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Eye disorders
Scleral hyperaemia
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Constipation
|
40.0%
2/5 • up to 8.5 months
|
75.0%
3/4 • up to 8.5 months
|
35.5%
11/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Anal fissure
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
1/5 • up to 8.5 months
|
50.0%
2/4 • up to 8.5 months
|
29.0%
9/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • up to 8.5 months
|
75.0%
3/4 • up to 8.5 months
|
67.7%
21/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
32.3%
10/31 • up to 8.5 months
|
|
General disorders
Fatigue
|
60.0%
3/5 • up to 8.5 months
|
100.0%
4/4 • up to 8.5 months
|
54.8%
17/31 • up to 8.5 months
|
|
General disorders
Infusion site irritation
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
General disorders
Local swelling
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
General disorders
Catheter site pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
General disorders
Chest pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
General disorders
Chills
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
General disorders
Influenza like illness
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
General disorders
Oedema peripheral
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
16.1%
5/31 • up to 8.5 months
|
|
General disorders
Pain
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
General disorders
Pyrexia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
19.4%
6/31 • up to 8.5 months
|
|
Infections and infestations
Escherichia urinary tract infection
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Infections and infestations
Influenza
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Infections and infestations
Nail bed infection
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Infections and infestations
Skin infection
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
1/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
29.0%
9/31 • up to 8.5 months
|
|
Infections and infestations
Catheter site cellulitis
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Infections and infestations
Gastrointestinal bacterial infection
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
19.4%
6/31 • up to 8.5 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Injury, poisoning and procedural complications
Contusion
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Injury, poisoning and procedural complications
Thermal burn
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Investigations
Haemoglobin decreased
|
20.0%
1/5 • up to 8.5 months
|
75.0%
3/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Investigations
Blood calcium decreased
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Investigations
Blood creatinine increased
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Investigations
Blood glucose increased
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Investigations
Blood magnesium decreased
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Investigations
Blood potassium decreased
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Investigations
Cardiac murmur
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Investigations
Hematocrit decreased
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Investigations
Weight decreased
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
20.0%
1/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
35.5%
11/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
60.0%
3/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
19.4%
6/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
60.0%
3/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
20.0%
1/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.0%
1/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
16.1%
5/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
19.4%
6/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Muscularskeletal discomfort
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Muscularskeletal pain
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Nervous system disorders
Headache
|
20.0%
1/5 • up to 8.5 months
|
50.0%
2/4 • up to 8.5 months
|
16.1%
5/31 • up to 8.5 months
|
|
Nervous system disorders
Neuropathy peripheral
|
20.0%
1/5 • up to 8.5 months
|
50.0%
2/4 • up to 8.5 months
|
32.3%
10/31 • up to 8.5 months
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Nervous system disorders
Tremor
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
12.9%
4/31 • up to 8.5 months
|
|
Reproductive system and breast disorders
Breast tenderness
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
40.0%
2/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
19.4%
6/31 • up to 8.5 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
9.7%
3/31 • up to 8.5 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
16.1%
5/31 • up to 8.5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
20.0%
1/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Nail growth abnormal
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Precancerous skin lesion
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Skin and subcutaneous tissue disorders
Skin atrophy
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
3.2%
1/31 • up to 8.5 months
|
|
Vascular disorders
Hot flush
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
0.00%
0/31 • up to 8.5 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/5 • up to 8.5 months
|
25.0%
1/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
|
Vascular disorders
Vein pain
|
0.00%
0/5 • up to 8.5 months
|
0.00%
0/4 • up to 8.5 months
|
6.5%
2/31 • up to 8.5 months
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER