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OPTIMAL: Optimising Renal Outcome in Myeloma Renal Failure

Sponsor
Oxford University Hospitals NHS Trust (Other)
Overall Status
Completed
CT.gov ID
NCT02424851
Collaborator
Janssen-Cilag Ltd. (Industry), Bloodwise (Other), University of Warwick (Other), University of Birmingham (Other)
31
Enrollment
9
Locations
2
Arms
65.6
Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness of bortezomib versus thalidomide in reducing free light chains in the blood of myeloma patients. In addition participants will receive bendamustine (chemotherapy) and dexamethasone (steroids), which increase the effectiveness of both bortezomib and thalidomide. The trial will also study whether an earlier reduction of free light chains increases the chances of the kidneys recovering.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Renal impairment is a life threatening condition of myeloma. 20-25% of patients will present at diagnosis with renal dysfunction. Outcome is poor due to high early mortality, with 28% of newly diagnosed myeloma patients in myeloma trials with renal failure not surviving beyond 100 days, compared with 10% overall.

This study aims to establish:

  1. Whether proteosomal inhibition (bortezomib) or immunomodulatory (thalidomide) based therapy achieves threshold reduction of serum free light chains (sFLCs) in a significant majority of patients.

  2. Whether sFLC response to the first 2 cycles (early responder) predicts haematological and renal response to the next 2 cycles of therapy.

  3. An early time point for assessment of sFLC reduction as a biomarker for response.

Participants will be stratified by age and chronic kidney disease (CKD) stage to receive either bortezomib, bendamustine and dexamethasone (BBD) or thalidomide, bendamustine and dexamethasone (BTD).

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study of Thalidomide, Bendamustine and Dexamethasone (BTD) Versus Bortezomib, Bendamustine and Dexamethasone (BBD) in Patients With Renal Failure Defined as a GFR Below 30 Mls/Min
Study Start Date :
Nov 1, 2014
Actual Primary Completion Date :
Apr 20, 2020
Actual Study Completion Date :
Apr 20, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A (BBD)

Bortezomib, Bendamustine and Dexamethasone

Drug: Bortezomib
1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib
Other Names:
  • Velcade

    • Drug: Bendamustine
    60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)

    Drug: Dexamethasone
    40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Active Comparator: Arm B (BTD)

    Thalidomide, Bendamustine and Dexamethasone

    Drug: Thalidomide
    100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)

    Drug: Bendamustine
    60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)

    Drug: Dexamethasone
    40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With >50% Reduction From Baseline in Serum Free Light Chain [End of week 6 (after receiving two cycles of therapy)]

    2. Number of Participants With Different Renal Responses to Treatment [End of week 12 (after receiving 4 cycles of therapy)]

    Secondary Outcome Measures

    1. Haematological and Non-haematological Toxicity in Both Treatment Arms [End of weeks 3, 6, 9, 12 (after receiving 4 cycles of therapy), 30 days after final treatment and 12 months after randomisation]

    2. Overall Survival [1 month post end of treatment and 1 year post randomisation]

    3. Renal Response After Two Cycles of Trial Treatment [End of 2nd treatment cycle, week 6]

    4. Quality of Life Measured by the EQ-5D-3L Questionnaire at Baseline and 1 Month Follow up [Baseline and 1 month follow up]

      The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored on a scale of 1 to 3: 1 (no problems), 2 (some problems), and 3 (extreme problems). Higher score equates to a worse outcome. As stated in the official EQ-5D user guide, patient responses to the 5 questions were converted into a single index value as per Dolan P (1997). Modeling valuations for EuroQol health states. Med Care 35(11):1095-108. These index values, with country specific value sets, facilitate the calculation of quality-adjusted life years (QALYs) that are used to inform economic evaluations of health care interventions. In the UK, the values range from -0.594 to +1.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participant is willing and able to give informed consent for participation in the trial.

    • Patients attending NHS (National Health Service) Haemato-oncology centres.

    • Patients with newly diagnosed symptomatic myeloma.

    • Glomerular Filtration Rate (GFR) <30 mls/min.

    • Chronic kidney disease (CKD) staging is based on estimated or measured GFR. CKD stage 4 (15-29 ml/min) and CKD stage 5 (<15 ml/min) are eligible to enter the study. It is expected centres will consider use of fluid resuscitation and pulsed dose of steroid therapy in this group of patients to salvage renal function prior to trial screening.

    • A number of patients with newly diagnosed myeloma and renal failure will have a pre-existing medical condition (hypertension, diabetes etc.) causing renal damage. Where there is a medical condition (e.g. hypertension, diabetes) which may cause renal damage, there must have been a further decline (≥15 mls/min GFR) between previous steady state and the study screening.

    • Female participants of childbearing potential and male patients whose partner is a woman of childbearing potential must be prepared to use contraception in accordance with (and consent to) the Celgene-approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention Programme.

    • Women of childbearing potential must have a negative pregnancy test performed by a healthcare professional in accordance with the Celgene-approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention.

    • Free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, localised prostate cancer or carcinoma "in-situ" of the cervix or breast.

    • In the Investigator's opinion, is able and willing to comply with all trial requirements.

    • Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

    Exclusion Criteria:

    • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial or the female partner of a male participant planning a pregnancy during the course of the trial.

    • Known allergy to investigational drugs.

    • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

    • Any of the following laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 1.0 x10^9/L

    • Platelet count <75 x 10^9/L

    • Serum SGOT/AST or SGPT/ALT (serum glutamic oxaloacetic transaminase/aspartate aminotransferase or serum glutamic pyruvic transaminase/alanine aminotransferase) >3 x upper limit of normal.

    • Use of any standard/experimental anti-myeloma drug therapy excluding dexamethasone 14 days prior to trial entry.

    • CKD stages < 4.

    • Intention to use a physical method of serum free light chain removal such as plasma exchange or high cut off dialysis.

    • Grade 2 neuropathy or more (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.0) will preclude use of thalidomide and bortezomib.

    • Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

    • Contraindicated to receive either one of the study drugs, thalidomide, bortezomib, bendamustine based on the respective summary of product characteristics.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Basingstoke & North Hampshire Hospital Basingstoke United Kingdom
    2 Heartlands Hospitals Birmingham United Kingdom
    3 Kent & Canterbury Hospital Canterbury United Kingdom CT1 3NG
    4 St Helier Hospital Epsom United Kingdom
    5 Royal Liverpool Hospital Liverpool United Kingdom
    6 Kings College Hospital London United Kingdom
    7 Churchill Hospital Oxford United Kingdom OX3 7LE
    8 Queen Alexandra Hospital Portsmouth United Kingdom
    9 Great Western Hospital Swindon United Kingdom

    Sponsors and Collaborators

    • Oxford University Hospitals NHS Trust
    • Janssen-Cilag Ltd.
    • Bloodwise
    • University of Warwick
    • University of Birmingham

    Investigators

    • Principal Investigator: Karthik Ramasamy, National Health Service, United Kingdom

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Karthik Ramasamy, Dr., Oxford University Hospitals NHS Trust
    ClinicalTrials.gov Identifier:
    NCT02424851
    Other Study ID Numbers:
    • 26866138-MMY2070
    • 2012-003947-31
    First Posted:
    Apr 23, 2015
    Last Update Posted:
    Jan 27, 2022
    Last Verified:
    Jan 1, 2022
    Keywords provided by Karthik Ramasamy, Dr., Oxford University Hospitals NHS Trust
    myeloma
    multiple myeloma
    chronic kidney disease
    renal failure
    bortezomib
    Velcade
    thalidomide
    bendamustine
    dexamethasone
    serum free light chains
    proteosomal inhibition
    immunomodulatory
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Kidney Diseases
    Renal Insufficiency, Chronic
    Renal Insufficiency
    Thalidomide
    Dexamethasone
    Bortezomib
    Bendamustine Hydrochloride

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Period Title: Overall Study
    STARTED 16 15
    COMPLETED 14 12
    NOT COMPLETED 2 3

    Baseline Characteristics

    Arm/Group Title Arm A (BBD) Arm B (BTD) Total
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Total of all reporting groups
    Overall Participants 16 15 31
    Age, Customized (Count of Participants)
    ≤70 years
    8
    50%
    8
    53.3%
    16
    51.6%
    >70 years
    8
    50%
    7
    46.7%
    15
    48.4%
    Sex: Female, Male (Count of Participants)
    Female
    8
    50%
    6
    40%
    14
    45.2%
    Male
    8
    50%
    9
    60%
    17
    54.8%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United Kingdom
    16
    100%
    15
    100%
    31
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With >50% Reduction From Baseline in Serum Free Light Chain
    Description
    Time Frame End of week 6 (after receiving two cycles of therapy)

    Outcome Measure Data

    Analysis Population Description
    The primary endpoint of serum free light chain response was assessed in 30 patients where samples were available at screening and the end of two cycles of trial treatment.
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Measure Participants 16 14
    Count of Participants [Participants]
    13
    81.3%
    3
    20%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments
    Method Fisher Exact
    Comments
    2. Primary Outcome
    Title Number of Participants With Different Renal Responses to Treatment
    Description
    Time Frame End of week 12 (after receiving 4 cycles of therapy)

    Outcome Measure Data

    Analysis Population Description
    Renal response in accordance with IMWG criteria was assessed in 20 patients with eGFR and creatinine clearance data recorded at screening and at the end of four cycles of trial treatment.
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Measure Participants 16 15
    Complete/partial response
    5
    31.3%
    1
    6.7%
    Minor response
    3
    18.8%
    7
    46.7%
    No response
    3
    18.8%
    1
    6.7%
    Not evaluable
    5
    31.3%
    6
    40%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.02
    Comments
    Method Fisher Exact
    Comments
    3. Secondary Outcome
    Title Haematological and Non-haematological Toxicity in Both Treatment Arms
    Description
    Time Frame End of weeks 3, 6, 9, 12 (after receiving 4 cycles of therapy), 30 days after final treatment and 12 months after randomisation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Measure Participants 16 15
    Serious adverse events
    2
    0
    Adverse events
    3
    6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments Statistical analysis of SAEs.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value =0.48
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments Statistical analysis of AEs
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value =0.25
    Comments
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Overall Survival
    Description
    Time Frame 1 month post end of treatment and 1 year post randomisation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Measure Participants 16 15
    Count of Participants [Participants]
    9
    56.3%
    13
    86.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value = 0.31
    Comments
    Method Log Rank
    Comments
    5. Secondary Outcome
    Title Renal Response After Two Cycles of Trial Treatment
    Description
    Time Frame End of 2nd treatment cycle, week 6

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Measure Participants 15 13
    Partial response
    2
    12.5%
    0
    0%
    Minor response
    9
    56.3%
    7
    46.7%
    No repsonse
    4
    25%
    6
    40%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value =0.45
    Comments
    Method Fisher Exact
    Comments
    6. Secondary Outcome
    Title Quality of Life Measured by the EQ-5D-3L Questionnaire at Baseline and 1 Month Follow up
    Description The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored on a scale of 1 to 3: 1 (no problems), 2 (some problems), and 3 (extreme problems). Higher score equates to a worse outcome. As stated in the official EQ-5D user guide, patient responses to the 5 questions were converted into a single index value as per Dolan P (1997). Modeling valuations for EuroQol health states. Med Care 35(11):1095-108. These index values, with country specific value sets, facilitate the calculation of quality-adjusted life years (QALYs) that are used to inform economic evaluations of health care interventions. In the UK, the values range from -0.594 to +1.
    Time Frame Baseline and 1 month follow up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    Measure Participants 8 9
    Baseline
    0.72
    (0.15)
    0.69
    (0.35)
    1 month FU
    0.69
    (0.19)
    0.80
    (0.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (BBD), Arm B (BTD)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.33
    Comments
    Method t-test, 1 sided
    Comments

    Adverse Events

    Time Frame 4 years, 2 months.
    Adverse Event Reporting Description
    Arm/Group Title Arm A (BBD) Arm B (BTD)
    Arm/Group Description Bortezomib, Bendamustine and Dexamethasone Bortezomib: 1.3 mg/m2 subcutaneously* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). *intravenous infusion available in case of patient intolerance to subcutaneous bortezomib Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle Thalidomide, Bendamustine and Dexamethasone Thalidomide: 100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Bendamustine: 60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised) Dexamethasone: 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
    All Cause Mortality
    Arm A (BBD) Arm B (BTD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/16 (43.8%) 2/15 (13.3%)
    Serious Adverse Events
    Arm A (BBD) Arm B (BTD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/16 (68.8%) 9/15 (60%)
    Blood and lymphatic system disorders
    Anaemia 2/16 (12.5%) 2 0/15 (0%) 2
    Febrile neutropenia 0/16 (0%) 1/15 (6.7%) 1
    Cardiac disorders
    Atrial fibrillation 2/16 (12.5%) 2 0/15 (0%) 2
    Supraventricular tachycardia 0/16 (0%) 1/15 (6.7%) 1
    Gastrointestinal disorders
    Diarrhea 2/16 (12.5%) 2 1/15 (6.7%) 1
    Vomiting 1/16 (6.3%) 1 1/15 (6.7%) 1
    General disorders
    Edema limbs 1/16 (6.3%) 1 0/15 (0%) 1
    Fatigue 0/16 (0%) 1/15 (6.7%) 1
    Fever 0/16 (0%) 2/15 (13.3%) 3
    Infections and infestations
    Bone infection 1/16 (6.3%) 1 0/15 (0%) 1
    Bronchial infection 1/16 (6.3%) 2 0/15 (0%) 2
    Infection 0/16 (0%) 1/15 (6.7%) 1
    Lung infection 1/16 (6.3%) 1 3/15 (20%) 3
    Sepsis 2/16 (12.5%) 2 0/15 (0%) 2
    Skin infection 1/16 (6.3%) 1 0/15 (0%) 1
    Upper respiratory infection 2/16 (12.5%) 2 0/15 (0%) 2
    Urinary tract infection 0/16 (0%) 1/15 (6.7%) 1
    Injury, poisoning and procedural complications
    Fall 2/16 (12.5%) 2 0/15 (0%) 2
    Metabolism and nutrition disorders
    Hyperkalemia 0/16 (0%) 1/15 (6.7%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 1/16 (6.3%) 1 1/15 (6.7%) 1
    Flank pain 1/16 (6.3%) 1 0/15 (0%) 1
    Nervous system disorders
    Dizziness 0/16 (0%) 1/15 (6.7%) 1
    Stroke 0/16 (0%) 1/15 (6.7%) 1
    Syncope 1/16 (6.3%) 1 0/15 (0%) 1
    Transient ischemic attacks 1/16 (6.3%) 1 0/15 (0%) 1
    Psychiatric disorders
    Delirium 0/16 (0%) 1/15 (6.7%) 1
    Renal and urinary disorders
    Chronic kidney disease 0/16 (0%) 2/15 (13.3%) 2
    Hematuria 0/16 (0%) 1/15 (6.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/16 (0%) 1/15 (6.7%) 1
    Atelectasis 0/16 (0%) 1/15 (6.7%) 1
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/16 (0%) 1/15 (6.7%) 1
    Vascular disorders
    Hypotension 1/16 (6.3%) 1 1/15 (6.7%) 1
    Thromboembolic event 0/16 (0%) 1/15 (6.7%) 1
    Other (Not Including Serious) Adverse Events
    Arm A (BBD) Arm B (BTD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/16 (93.8%) 11/15 (73.3%)
    Blood and lymphatic system disorders
    Anemia 1/16 (6.3%) 1 3/15 (20%) 4
    Febrile Neutropenia 0/16 (0%) 1/15 (6.7%) 1
    Cardiac disorders
    Left Ventricular systolic dysfunction 0/16 (0%) 1/15 (6.7%) 1
    Eye disorders
    Conjunctivtis 1/16 (6.3%) 1 0/15 (0%) 1
    Blurred vision 1/16 (6.3%) 2 0/15 (0%) 2
    Eye disorders - Other, specify: visual disturbance? 0/16 (0%) 1/15 (6.7%) 1
    Gastrointestinal disorders
    Mucositis oral 1/16 (6.3%) 1 0/15 (0%) 1
    Dyspepsia 1/16 (6.3%) 2 0/15 (0%) 2
    Vomiting 3/16 (18.8%) 3 1/15 (6.7%) 1
    Nausea 4/16 (25%) 5 1/15 (6.7%) 1
    Diarrhea 3/16 (18.8%) 6 2/15 (13.3%) 3
    Constipation 4/16 (25%) 11 3/15 (20%) 3
    Dysphagia 0/16 (0%) 1/15 (6.7%) 1
    Oral Dysesthesia 0/16 (0%) 1/15 (6.7%) 1
    Stomach pain 0/16 (0%) 2/15 (13.3%) 2
    General disorders
    Fever 1/16 (6.3%) 1 1/15 (6.7%) 1
    Edema limbs 4/16 (25%) 4 3/15 (20%) 3
    Fatigue 4/16 (25%) 4 5/15 (33.3%) 9
    Infusion Site Extravasation 0/16 (0%) 1/15 (6.7%) 1
    Pain 0/16 (0%) 1/15 (6.7%) 1
    Infections and infestations
    Bone infection 1/16 (6.3%) 1 0/15 (0%) 1
    Bronchial Infection 1/16 (6.3%) 1 0/15 (0%) 1
    Catheter related infection 1/16 (6.3%) 1 0/15 (0%) 1
    Enterocolitis infectious 1/16 (6.3%) 1 0/15 (0%) 1
    Mucosal infection 1/16 (6.3%) 1 0/15 (0%) 1
    Papulopustular rash 1/16 (6.3%) 1 0/15 (0%) 1
    Skin infection 2/16 (12.5%) 2 1/15 (6.7%) 1
    Lung infection 2/16 (12.5%) 5 3/15 (20%) 5
    Infections and infestations - Other, specify: infection (unknown source) 0/16 (0%) 1/15 (6.7%) 1
    Infections and infestations - Other, specify: (Oral) thrush 0/16 (0%) 2/15 (13.3%) 2
    Injury, poisoning and procedural complications
    Fall 1/16 (6.3%) 1 1/15 (6.7%) 1
    Investigations
    Alanine aminotransferase increased 0/16 (0%) 1/15 (6.7%) 1
    Alkaline Phosphatase Increased 0/16 (0%) 1/15 (6.7%) 1
    Weight Loss 1/16 (6.3%) 1 1/15 (6.7%) 1
    Neutrophil count decreased 3/16 (18.8%) 3 2/15 (13.3%) 2
    Creatinine increased 0/16 (0%) 1/15 (6.7%) 1
    Lymphocyte count decreased 0/16 (0%) 2/15 (13.3%) 2
    White blood cell decreased 0/16 (0%) 2/15 (13.3%) 2
    Metabolism and nutrition disorders
    Anorexia 1/16 (6.3%) 1 0/15 (0%) 1
    Hypokalemia 1/16 (6.3%) 2 0/15 (0%) 2
    Hyperkalemia 0/16 (0%) 1/15 (6.7%) 1
    Hyponatremia 0/16 (0%) 1/15 (6.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthritis 0/16 (0%) 1/15 (6.7%) 1
    Chest wall pain 1/16 (6.3%) 1 0/15 (0%) 1
    Back pain 2/16 (12.5%) 3 0/15 (0%) 3
    Musculoskeletal and connective tissue disorder - Other, specify 0/16 (0%) 1/15 (6.7%) 1
    Pain in extremity 0/16 (0%) 1/15 (6.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: Labial cyst 1/16 (6.3%) 1 0/15 (0%) 1
    Nervous system disorders
    Tremor 1/16 (6.3%) 1 3/15 (20%) 4
    Syncope 1/16 (6.3%) 2 0/15 (0%) 2
    Dizziness 2/16 (12.5%) 2 1/15 (6.7%) 1
    Peripheral sensory neuropathy 2/16 (12.5%) 2 2/15 (13.3%) 5
    Paresthesia 2/16 (12.5%) 2 3/15 (20%) 3
    Presyncope 0/16 (0%) 1/15 (6.7%) 1
    Psychiatric disorders
    Anxiety 1/16 (6.3%) 1 0/15 (0%) 1
    Insomnia 1/16 (6.3%) 1 0/15 (0%) 1
    Renal and urinary disorders
    Acute Kidney Injury 0/16 (0%) 2/15 (13.3%) 2
    Chronic Kidney Disease 0/16 (0%) 1/15 (6.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/16 (0%) 1/15 (6.7%) 4
    Laryngeal hemorrhage 1/16 (6.3%) 1 0/15 (0%) 1
    Dyspnea 2/16 (12.5%) 2 1/15 (6.7%) 1
    Upper respiratory infection 2/16 (12.5%) 2 1/15 (6.7%) 1
    Productive cough 0/16 (0%) 1/15 (6.7%) 1
    Cough 0/16 (0%) 2/15 (13.3%) 2
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/16 (6.3%) 1 3/15 (20%) 8
    Skin ulceration 1/16 (6.3%) 2 0/15 (0%) 2
    Dry Skin 0/16 (0%) 1/15 (6.7%) 1
    Scalp pain 0/16 (0%) 1/15 (6.7%) 1
    Erythroderma 0/16 (0%) 1/15 (6.7%) 2
    Palmar-plantae erythrodysesthesia syndrome 0/16 (0%) 1/15 (6.7%) 2
    Vascular disorders
    Hypertension 0/16 (0%) 1/15 (6.7%) 1
    Hypotension 0/16 (0%) 1/15 (6.7%) 1
    Superficial thrombophlebitis 0/16 (0%) 1/15 (6.7%) 1
    Thromboembolic event 0/16 (0%) 1/15 (6.7%) 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 Richard Brouwer
    Organization Oxford University Hospitals NHS Foundation Trust
    Phone 441865226950
    Email richard.brouwer@ouh.nhs.uk
    Responsible Party:
    Karthik Ramasamy, Dr., Oxford University Hospitals NHS Trust
    ClinicalTrials.gov Identifier:
    NCT02424851
    Other Study ID Numbers:
    • 26866138-MMY2070
    • 2012-003947-31
    First Posted:
    Apr 23, 2015
    Last Update Posted:
    Jan 27, 2022
    Last Verified:
    Jan 1, 2022