Bendamustine Hydrochloride, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
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.
-
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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. |
Drug: Bendamustine hydrochloride
Given IV
Other Names:
Drug: Bortezomib
Given SC
Other Names:
Drug: Dexamethasone
Given PO
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
-
= 18 years of age
-
ECOG <= 3
-
Signed informed consent
-
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:
-
Failure to sign informed consent
-
Smoldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), or plasma cell leukemia
-
History of previously treated smoldering myeloma
-
Grade 3 or above peripheral neuropathy
-
Uncontrolled human immunodeficiency virus (HIV)
-
Active hepatitis A, B or C
-
Pregnant or lactating females
-
Total bilirubin >3 times the upper limit of normal
-
ASLT/ALT > 2.5 times the upper limit of normal
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
Sponsors and Collaborators
- Sidney Kimmel Cancer Center at Thomas Jefferson University
Investigators
- Principal Investigator: Joanne Filicko-O'Hara, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
- Jefferson University Hospitals
Publications
None provided.- 14D.300
- 2014-025
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Period Title: Overall Study | |
STARTED | 24 |
COMPLETED | 24 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Overall Participants | 24 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
18
75%
|
>=65 years |
6
25%
|
Sex: Female, Male (Count of Participants) | |
Female |
16
66.7%
|
Male |
8
33.3%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
0
0%
|
Not Hispanic or Latino |
24
100%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
14
58.3%
|
White |
10
41.7%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
24
100%
|
Outcome Measures
Title | Count of Participants That Experience Overall Response Following 4 Cycles of the Combination Regimen BBd |
---|---|
Description | ORR (partial remission or better) to induction therapy following 4 cycles of the combination regimen BBd. |
Time Frame | At least 140 days |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Measure Participants | 20 |
Count of Participants [Participants] |
13
54.2%
|
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Measure Participants | 20 |
Number [Adverse Events] |
22
|
Title | Count of Participants That Experience Very Good Partial Remission (VGPR) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Measure Participants | 20 |
Count of Participants [Participants] |
9
37.5%
|
Title | Count of Participants That Experience Progression-free Survival (PFS) |
---|---|
Description | The amount of participants that survive one year after treatment with BBd and do not experience worsening disease. |
Time Frame | 1 year |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Measure Participants | 20 |
Count of Participants [Participants] |
2
8.3%
|
Title | Count of Participants That Experience Overall Survival (OS) |
---|---|
Description | The amount of participants that start treatment with BBd and survive at least one year post treatment completion. |
Time Frame | 1 year |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) |
---|---|
Arm/Group Description | 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 |
Measure Participants | 20 |
Count of Participants [Participants] |
2
8.3%
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Bendamustine, Bortezomib, Dexamethasone (Standard) | |
Arm/Group Description | 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 | |
All Cause Mortality |
||
Bendamustine, Bortezomib, Dexamethasone (Standard) | ||
Affected / at Risk (%) | # Events | |
Total | 1/24 (4.2%) | |
Serious Adverse Events |
||
Bendamustine, Bortezomib, Dexamethasone (Standard) | ||
Affected / at Risk (%) | # Events | |
Total | 9/24 (37.5%) | |
Blood and lymphatic system disorders | ||
Hypercalcemia | 1/24 (4.2%) | 1 |
Gout | 1/24 (4.2%) | 1 |
Syncope episode | 1/24 (4.2%) | 3 |
General disorders | ||
Failure to Thrive | 1/24 (4.2%) | 1 |
Hepatobiliary disorders | ||
Acute kidney injury | 1/24 (4.2%) | 2 |
Immune system disorders | ||
Death- Anaphylactic Shock | 1/24 (4.2%) | 1 |
Allergic Reaction | 1/24 (4.2%) | 1 |
Infections and infestations | ||
Febrile Neutropenia | 1/24 (4.2%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Joint Function Pain | 1/24 (4.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Pneumonia | 1/24 (4.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Bendamustine, Bortezomib, Dexamethasone (Standard) | ||
Affected / at Risk (%) | # Events | |
Total | 24/24 (100%) | |
Blood and lymphatic system disorders | ||
Alkaline Phosphate increased | 7/24 (29.2%) | 9 |
Anemia | 12/24 (50%) | 16 |
AST increase | 2/24 (8.3%) | 2 |
Creatinine increased | 2/24 (8.3%) | 2 |
Epistaxis | 1/24 (4.2%) | 1 |
Hypercalcemia | 4/24 (16.7%) | 4 |
Hyperglycemia | 4/24 (16.7%) | 4 |
Hyperkalemia | 3/24 (12.5%) | 3 |
Hypermagnesemia | 1/24 (4.2%) | 1 |
Hypertension | 3/24 (12.5%) | 3 |
Hyperuricemia | 3/24 (12.5%) | 3 |
Hypoalbuminemia | 3/24 (12.5%) | 3 |
Hypocalcemia | 5/24 (20.8%) | 5 |
Hypokalemia | 3/24 (12.5%) | 4 |
Hypomagnesium | 2/24 (8.3%) | 2 |
Hyponatremia | 3/24 (12.5%) | 3 |
Hypophosphatemia | 4/24 (16.7%) | 5 |
Hypotension | 2/24 (8.3%) | 2 |
Lymphocyte count decreased | 6/24 (25%) | 15 |
Orthostatic hypotension | 1/24 (4.2%) | 1 |
Platelet Count decreased | 2/24 (8.3%) | 3 |
White blood cell count decreased | 7/24 (29.2%) | 14 |
ANC increased | 1/24 (4.2%) | 1 |
Cardiac disorders | ||
Palpitations | 1/24 (4.2%) | 1 |
Ear and labyrinth disorders | ||
Ear infection | 1/24 (4.2%) | 2 |
Eye disorders | ||
Conjuctivitis | 1/24 (4.2%) | 1 |
Decreased Visual Field | 1/24 (4.2%) | 1 |
Gastrointestinal disorders | ||
Abdominal cramping | 1/24 (4.2%) | 1 |
Constipation | 6/24 (25%) | 6 |
Diarrhea | 5/24 (20.8%) | 8 |
Dysphagia | 1/24 (4.2%) | 1 |
Gastroesophageal reflux disease | 3/24 (12.5%) | 3 |
Nausea | 9/24 (37.5%) | 10 |
Stomach Pain | 1/24 (4.2%) | 1 |
Indigestion | 1/24 (4.2%) | 1 |
General disorders | ||
Change in taste | 4/24 (16.7%) | 4 |
Confusion | 1/24 (4.2%) | 1 |
Dry mouth | 2/24 (8.3%) | 2 |
Edema | 4/24 (16.7%) | 4 |
Fatigue | 13/24 (54.2%) | 14 |
Hand pain | 1/24 (4.2%) | 1 |
Headache | 3/24 (12.5%) | 4 |
Hiccups | 1/24 (4.2%) | 2 |
Hot flashes | 1/24 (4.2%) | 1 |
Insomnia | 3/24 (12.5%) | 3 |
Light headedness | 1/24 (4.2%) | 1 |
Loss of appetite | 2/24 (8.3%) | 2 |
Nasal Congestion | 2/24 (8.3%) | 2 |
Pain | 3/24 (12.5%) | 4 |
Pain at port site | 1/24 (4.2%) | 1 |
Pain Knee | 1/24 (4.2%) | 2 |
Pain shoulder | 1/24 (4.2%) | 1 |
Pain- side of face | 1/24 (4.2%) | 1 |
Rib pain | 2/24 (8.3%) | 2 |
Sore Throat | 2/24 (8.3%) | 2 |
Soreness | 1/24 (4.2%) | 2 |
Fall | 1/24 (4.2%) | 1 |
Allergic Rhinitis | 1/24 (4.2%) | 1 |
Hepatobiliary disorders | ||
Acute kidney injury | 1/24 (4.2%) | 1 |
Immune system disorders | ||
Flu like symptoms | 1/24 (4.2%) | 1 |
Infections and infestations | ||
Infection site reaction | 4/24 (16.7%) | 4 |
Sinusitis | 1/24 (4.2%) | 2 |
Gum infection | 1/24 (4.2%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Back pain | 8/24 (33.3%) | 8 |
Chest pain | 1/24 (4.2%) | 1 |
Leg Pain (spasm) | 1/24 (4.2%) | 1 |
Weakness | 1/24 (4.2%) | 1 |
Neck pain | 1/24 (4.2%) | 1 |
Flank pain | 1/24 (4.2%) | 1 |
Nervous system disorders | ||
Neuropathy | 2/24 (8.3%) | 2 |
Paresthesia | 1/24 (4.2%) | 1 |
peripheral motor neuropathy | 1/24 (4.2%) | 1 |
Psychiatric disorders | ||
Anorexia | 5/24 (20.8%) | 5 |
Depression | 3/24 (12.5%) | 3 |
Renal and urinary disorders | ||
Urinary Frequency | 2/24 (8.3%) | 2 |
Urinary Tract infection | 1/24 (4.2%) | 1 |
Hematuria | 2/24 (8.3%) | 2 |
Reproductive system and breast disorders | ||
Swelling L- Breast | 1/24 (4.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Dry cough | 3/24 (12.5%) | 3 |
Dyspnea | 5/24 (20.8%) | 6 |
Productive Cough | 1/24 (4.2%) | 1 |
Skin and subcutaneous tissue disorders | ||
Alopecia | 1/24 (4.2%) | 1 |
Bruising | 2/24 (8.3%) | 2 |
Dry skin | 1/24 (4.2%) | 1 |
Rash unspecified | 1/24 (4.2%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Joanne Filicko, O'Hara |
---|---|
Organization | Sidney Kimmel Cancer Center at Thomas Jefferson University |
Phone | 215-955-8874 |
joanne.filicko@jeffersron.edu |
- 14D.300
- 2014-025