Stage III Multiple Myeloma, Stage II Multiple Myeloma, Stage I Multiple Myeloma
Conditions
Brief summary
This phase II trial studies side effects and how well bendamustine hydrochloride, bortezomib, and dexamethasone work in treating patients with newly diagnosed multiple myeloma. Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bendamustine hydrochloride with bortezomib and dexamethasone may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. Establish the response rate of induction therapy following 4 cycles of the combination regimen bendamustine (bendamustine hydrochloride), bortezomib and dexamethasone (BBd) in patients with newly diagnosed multiple myeloma. II. Describe the tolerability and toxicities of this regimen. III. Provide one-year progression-free survival and one-year overall survival data following this therapeutic strategy. OUTLINE: Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and 2; bortezomib subcutaneously (SC) on days 1, 8, 15, and 22; and dexamethasone orally (PO) on days 1, 8, 15, and 22. Treatment repeats every 35 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than a very good partial response (VGPR) or with more than 10% bone marrow plasmacytosis may receive 2 additional courses. NOTE: Patients requiring immediate reduction in paraprotein during course 1 only receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2; bortezomib IV on days 1, 4, 8, and 11; and dexamethasone PO on days 1-4. After completion of study treatment, patients are followed up for 1 year.
Interventions
DRUGBendamustine hydrochloride
Given IV
DRUGBortezomib
Given SC
DRUGDexamethasone
Given PO
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. New diagnosis of multiple myeloma with no prior history of systemic treatment (Exceptions include corticosteroids, bisphosphonates, single agent cyclophosphamide, \<= 21 days of the first cycle of a planned regimen 2. \>= 18 years of age 3. ECOG \<= 3 4. Signed informed consent 5. Measurable serum paraprotein on SPEP or serum free light chains and ratio, or quantifiable Bence-Jones proteinuria on 24 hour urine specimen. If the monoclonal protein has merged with the beta region we will follow the serum immunoglobulin of the involved heavy chain and comment on either partial remission (PR, as judged by two protocol investigators) or complete remission (CR, as defined by the achievement of PR as above and the resolution of the monoclonal protein by immunofixation in the serum and urine.)
Exclusion criteria
1. Failure to sign informed consent 2. Smoldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), or plasma cell leukemia 3. History of previously treated smoldering myeloma 4. Grade 3 or above peripheral neuropathy 5. Uncontrolled human immunodeficiency virus (HIV) 6. Active hepatitis A, B or C 7. Pregnant or lactating females 8. Total bilirubin \>3 times the upper limit of normal 9. ASLT/ALT \> 2.5 times the upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants That Experience Overall Response Following 4 Cycles of the Combination Regimen BBd | At least 140 days | ORR (partial remission or better) to induction therapy following 4 cycles of the combination regimen BBd. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants That Experience Overall Survival (OS) | 1 year | The amount of participants that start treatment with BBd and survive at least one year post treatment completion. |
| Incidence of Grade 3-4 Adverse Events From the Combination of Bendamustine Hydrochloride, Bortezomib, and Dexamethasone Based on the Common Terminology Criteria Version 4.0 | Up to 1 year | All adverse events are tracked during the course of the trial. Adverse events with a grade of 3-4 will be tracked and recorded. |
| Count of Participants That Experience Very Good Partial Remission (VGPR) | Up to 1 year | Very good partial remission (VGPR) to induction therapy following 4 cycles of the combination regimen BBd. As defined as no dectable M-protein on SPEP (Serum protein electrophoresis) but positive IFX (Immunofixation) on serum or urine and \>90% reduction of M-protein in serum and urine |
| Count of Participants That Experience Progression-free Survival (PFS) | 1 year | The amount of participants that survive one year after treatment with BBd and do not experience worsening disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bendamustine, Bortezomib, Dexamethasone (Standard) Patients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2; bortezomib SC on days 1, 8, 15, and 22; and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 35 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than a VGPR or with more than 10% bone marrow plasmacytosis may receive 2 additional courses.
Bendamustine hydrochloride: Given IV
Bortezomib: Given SC
Dexamethasone: Given PO | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Bendamustine, Bortezomib, Dexamethasone (Standard) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 24 |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 9 / 24 |
Outcome results
Primary
Count of Participants That Experience Overall Response Following 4 Cycles of the Combination Regimen BBd
ORR (partial remission or better) to induction therapy following 4 cycles of the combination regimen BBd.
Time frame: At least 140 days
Population: 4 subjects were not evaluable - (1 didn't get any therapy on study, 1 received only first cycle and 2 developed medical issues that took them off study during the first cycle)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bendamustine, Bortezomib, Dexamethasone (Standard) | Count of Participants That Experience Overall Response Following 4 Cycles of the Combination Regimen BBd | 13 Participants |
Secondary
Count of Participants That Experience Overall Survival (OS)
The amount of participants that start treatment with BBd and survive at least one year post treatment completion.
Time frame: 1 year
Population: 4 were not evaluable - (1 didn't get any therapy on study, 1 received only first cycle and 2 developed medical issues that took them off study during the first cycle)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bendamustine, Bortezomib, Dexamethasone (Standard) | Count of Participants That Experience Overall Survival (OS) | 2 Participants |
Secondary
Count of Participants That Experience Progression-free Survival (PFS)
The amount of participants that survive one year after treatment with BBd and do not experience worsening disease.
Time frame: 1 year
Population: 4 were not evaluable - (1 didn't get any therapy on study, 1 received only first cycle and 2 developed medical issues that took them off study during the first cycle)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bendamustine, Bortezomib, Dexamethasone (Standard) | Count of Participants That Experience Progression-free Survival (PFS) | 2 Participants |
Secondary
Count of Participants That Experience Very Good Partial Remission (VGPR)
Very good partial remission (VGPR) to induction therapy following 4 cycles of the combination regimen BBd. As defined as no dectable M-protein on SPEP (Serum protein electrophoresis) but positive IFX (Immunofixation) on serum or urine and \>90% reduction of M-protein in serum and urine
Time frame: Up to 1 year
Population: 4 were not evaluable - (1 didn't get any therapy on study, 1 received only first cycle and 2 developed medical issues that took them off study during the first cycle)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bendamustine, Bortezomib, Dexamethasone (Standard) | Count of Participants That Experience Very Good Partial Remission (VGPR) | 9 Participants |
Secondary
Incidence of Grade 3-4 Adverse Events From the Combination of Bendamustine Hydrochloride, Bortezomib, and Dexamethasone Based on the Common Terminology Criteria Version 4.0
All adverse events are tracked during the course of the trial. Adverse events with a grade of 3-4 will be tracked and recorded.
Time frame: Up to 1 year
Population: 4 were not evaluable - (1 didn't get any therapy on study, 1 received only first cycle and 2 developed medical issues that took them off study during the first cycle)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bendamustine, Bortezomib, Dexamethasone (Standard) | Incidence of Grade 3-4 Adverse Events From the Combination of Bendamustine Hydrochloride, Bortezomib, and Dexamethasone Based on the Common Terminology Criteria Version 4.0 | 22 Adverse Events |