Bendamustine Hydrochloride, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
Overall Status
Completed
CT.gov ID
NCT02224729
Collaborator
(none)
24
1
1
50.8
0.5

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:
  1. 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.

  2. 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

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Bendamustine, Bortezomib, and Dexamethasone (BBD) for Newly Diagnosed Patients With Multiple Myeloma
Actual Study Start Date :
Aug 25, 2014
Actual Primary Completion Date :
Apr 21, 2016
Actual Study Completion Date :
Nov 17, 2018

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:
  • Treakisym
  • Ribomustin
  • Levact
  • Treanda
  • SDX-105
  • Drug: Bortezomib
    Given SC
    Other Names:
  • PS-341
  • Velcade
  • Cytomib
  • Drug: Dexamethasone
    Given PO

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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

    3. 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.

    4. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    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:

    Publications

    None provided.
    Responsible Party:
    Sidney Kimmel Cancer Center at Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT02224729
    Other Study ID Numbers:
    • 14D.300
    • 2014-025
    First Posted:
    Aug 25, 2014
    Last Update Posted:
    Sep 13, 2019
    Last Verified:
    Aug 1, 2019

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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%
    4. Secondary Outcome
    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%
    5. Secondary Outcome
    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

    [Not Specified]

    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
    Email joanne.filicko@jeffersron.edu
    Responsible Party:
    Sidney Kimmel Cancer Center at Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT02224729
    Other Study ID Numbers:
    • 14D.300
    • 2014-025
    First Posted:
    Aug 25, 2014
    Last Update Posted:
    Sep 13, 2019
    Last Verified:
    Aug 1, 2019