Trial Outcomes & Findings for Study to Evaluate the Combination of Bendamustine, Bortezomib and Dexamethasone (BBD) in the First-Line Treatment of Patients With Multiple Myeloma Who Are Not Candidates for High Dose Chemotherapy (NCT NCT01056276)

Last Updated: 2017-05-03

Results Overview

Defined as the percent of patients having a complete response (CR) to treatment, assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. CR=disappearance of soft tissue plasmacytomas and 5% or less plasma cells in bone marrow.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

every 8 weeks for approximately 48 months

Results posted on

2017-05-03

Participant Flow

Between May 2010 and May 2014, 59 patients with transplant-ineligible Multiple Myeloma (MM) were enrolled at 9 investigational sites in the U.S. The original treatment plan was modified during the trial to decrease intensity but increase treatment duration. Of 59 enrolled patients, 18 were treated on the initial regimen; 41 on the modified plan.

Participant milestones

Participant milestones
Measure	Original BBD Regimen Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Treatment: Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Treatment Period-Cycles 1-8 STARTED	18	41
Treatment Period-Cycles 1-8 COMPLETED	5	33
Treatment Period-Cycles 1-8 NOT COMPLETED	13	8
Maintenance Therapy STARTED	0	28
Maintenance Therapy COMPLETED	0	0
Maintenance Therapy NOT COMPLETED	0	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Original BBD Regimen Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Treatment: Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Treatment Period-Cycles 1-8 Toxicity	2	1
Treatment Period-Cycles 1-8 Withdrawal by Subject	1	2
Treatment Period-Cycles 1-8 Disease Progression	2	2
Treatment Period-Cycles 1-8 Intercurrent Illness	1	2
Treatment Period-Cycles 1-8 Physician Decision	3	0
Treatment Period-Cycles 1-8 Death	3	1
Treatment Period-Cycles 1-8 Lost to Follow-up	1	0
Maintenance Therapy Toxicity	0	2
Maintenance Therapy Progressive Disease	0	9
Maintenance Therapy Physician Decision	0	1
Maintenance Therapy Withdrawal by Subject	0	1
Maintenance Therapy Intercurrent Illness	0	1
Maintenance Therapy Continuing maintenance therapy	0	14

Baseline Characteristics

Study to Evaluate the Combination of Bendamustine, Bortezomib and Dexamethasone (BBD) in the First-Line Treatment of Patients With Multiple Myeloma Who Are Not Candidates for High Dose Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Original BBD Regimen n=18 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen n=41 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Treatment: Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15	Total n=59 Participants Total of all reporting groups
Age, Continuous	75 years n=5 Participants	75 years n=7 Participants	75 years n=5 Participants
Sex/Gender, Customized female	5 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants
Sex/Gender, Customized male	13 Participants n=5 Participants	26 Participants n=7 Participants	39 Participants n=5 Participants
Sex/Gender, Customized unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	3 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	14 Participants n=5 Participants	27 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	41 participants n=7 Participants	59 participants n=5 Participants

PRIMARY outcome

Timeframe: every 8 weeks for approximately 48 months

Population: All patients evaluable for response.

Outcome measures

Outcome measures
Measure	Original BBD Regimen n=17 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen n=39 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Complete Response Rate	0 percentage of participants	13 percentage of participants

PRIMARY outcome

Timeframe: approximately 36 weeks

Population: All patients who received at least one dose of BBD treatment.

All serious adverse events (SAEs) and non-serious adverse events (AEs) were assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0, and were collected from start of study treatment until 30 days after last dose of study medication. Refer to the Adverse Event module for specific terms.

Outcome measures

Outcome measures
Measure	Original BBD Regimen n=18 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen n=41 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Number of Patients Who Experienced Serious and Non-serious Adverse Events SAEs	7 participants	17 participants
Number of Patients Who Experienced Serious and Non-serious Adverse Events AEs	18 participants	38 participants

SECONDARY outcome

Timeframe: every 8 weeks for up to 48 months

Defined as the interval of time (in months) that patient are alive from date of first protocol treatment to date of documented tumor progression or date of death from any cause. Progressive disease, assessed according to International Myeloma Working Group Uniform Response Criteria, is defined as at least a 25% increase from the nadir in any one of the following criteria: serum M-protein, urine M-protein, or bone marrow plasma cell percentage of 10% or greater.

Outcome measures

Outcome measures
Measure	Original BBD Regimen n=17 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen n=39 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Progression Free Survival	11.1 months Interval 5.5 to 16.3	18.9 months Interval 14.1 to 31.8

SECONDARY outcome

Timeframe: every 4 weeks until progressive disease then every 12 weeks, projected 48 months

Population: All patients evaluable for response.

Defined as the interval of time, in months, from first study treatment until the earlier of the date of death or date last known alive.

Outcome measures

Outcome measures
Measure	Original BBD Regimen n=17 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen n=39 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Overall Survival	NA months Median overall survival has not been reached.	NA months Median overall survival has not been reached..

SECONDARY outcome

Timeframe: every 4 weeks for approximately 2 years

Population: All patients evaluable for response.

The number of patients with observed complete or partial response (CR or PR) assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria. PR=50% or greater reduction from baseline in serum M-protein and 90% or greater reduction from baseline in 24-hour urinary M-protein.

Outcome measures

Outcome measures
Measure	Original BBD Regimen n=17 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. No maintenance therapy. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 4 Bortezomib: 1.3 mg/m2 IV Days 1, 4, 8, 11 Dexamethasone: 40 mg orally (PO) Days 1, 2, 3, 4	Modified BBD Regimen n=39 Participants Bendamustine, Bortezomib,and Dexamethasone (BBD) every 28 days for 8 cycles or 2 cycles beyond a confirmed complete response, assessed by International Myeloma Working Group (IMWG) Uniform Response Criteria criteria. Patients with stable disease and no intolerable toxicity may continue maintenance therapy with Bortezomib and Dexamethasone every 28 days for 4 cycles. After cycle 4, dexamethasone may be discontinued at the physician's discretion. Bendamustine: 80 mg/m2 via intravenous (IV) Days 1 and 2 Bortezomib: 1.3 mg/m2 IV Days 1, 8, 15 Dexamethasone: 20 mg orally (PO) Days 1, 2, 8, 9, 15,16 Maintenance: Bortezomib: 1.3 mg/m2 IV or SQ Days 1, 15 Dexamethasone: 20 mg PO Days 1, 15
Overall Response Rate CR	0 participants	5 participants
Overall Response Rate PR	5 participants	8 participants

Adverse Events

Original BBD Regimen

Serious events: 7 serious events

Other events: 18 other events

Deaths: 0 deaths

Modified BBD Regimen

Serious events: 17 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Charles Davis, RAC

Sarah Cannon Development Innovations

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Publication restrictions are in place

Restriction type: OTHER