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A Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (AMBER) (AMBER)

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Bevacizumab
Bortezomib
placebo
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Avastin, AMBER, Myeloma, Velcade

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Previously diagnosed with multiple myeloma
  • Relapsed or refractory multiple myeloma with disease progression following one to three prior treatment regimens
  • Measurable multiple myeloma disease

Exclusion Criteria:

  • Grade ≥ 2 peripheral neuropathy
  • Use of corticosteroids within 21 days prior to Day 1
  • Use of other anti-myeloma therapy within 21 days prior to Day 1
  • Intolerance to bortezomib or compounds containing boron
  • Life expectancy of < 12 weeks
  • Current, recent, or planned participation in an experimental drug study
  • Active malignancy other than multiple myeloma within 5 years before screening
  • Prior treatment with bevacizumab
  • Inadequately controlled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
  • Decreased left ventricular function at study entry
  • History of myocardial infarction or unstable angina within 6 months prior to Day 1
  • History of stroke or transient ischemic attack within 6 months prior to Day 1
  • Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to Day 1
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, including placement of a vascular access device within 7 days prior to Day 1
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture (for pathologic bone fractures consistent with multiple myeloma, patients may be eligible if no treatment is planned)
  • Albuminuria
  • Known hypersensitivity to any component of bevacizumab
  • Pregnancy (positive pregnancy test) or lactation

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Bortezomib + bevacizumab

    Bortezomib + placebo

    Arm Description

    Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.

    Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.

    Outcomes

    Primary Outcome Measures

    Progression-free Survival (PFS)
    Progression-free survival (PFS) was defined as the time from randomization to disease progression or death on study from any cause within 30 days of the last response assessment. Disease progression was determined by the investigator using the International Myeloma Working Group's (IMWG) uniform response criteria. Median PFS was estimated using Kaplan-Meier methodology. For patients who were alive at the time of the analysis and whose disease had not yet progressed, PFS was censored at the time of the last response assessment.

    Secondary Outcome Measures

    Number of Participants With an Overall Response
    Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR, respectively) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the International Myeloma Working Group's (IMWG's) uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.
    Percentage of Participants With an Overall Response
    Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the IMWG's uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.
    Duration of Response
    Duration of response was defined as the time from the initial response to disease progression or death on study. Disease progression was determined by the investigator using the IMWG's uniform response criteria and defined as an increase of ≥25% from best response in: Serum M-protein and/or Urine M-protein and/or Marrow plasma cells; or new or increased plasmacytomas or bone lesions; or hypercalcemia due to myeloma. Duration of response was estimated using Kaplan-Meier. For patients who had not progressed or died, duration of response was censored at the date of the last response assessment.
    Overall Survival (OS)
    Overall survival was defined as the duration of time from randomization until death from any cause. All deaths were included, whether they occurred on study treatment or following treatment discontinuation. Overall survival was estimated using Kaplan-Meier. For patients who had not died, overall survival was censored at the date that the patient was last known to be alive.
    Number of Participants With Selected Adverse Events (AEs)
    Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. All serious adverse events are listed in the Adverse Event Reporting section.

    Full Information

    First Posted
    May 14, 2007
    Last Updated
    May 19, 2017
    Sponsor
    Genentech, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00473590
    Brief Title
    A Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (AMBER)
    Acronym
    AMBER
    Official Title
    A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2007 (Actual)
    Primary Completion Date
    November 2009 (Actual)
    Study Completion Date
    November 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Genentech, Inc.

    4. Oversight

    5. Study Description

    Brief Summary
    This is a randomized, blinded, placebo-controlled, multicenter, Phase II study designed to provide a preliminary assessment of the safety and efficacy of combining bevacizumab with bortezomib in patients with relapsed or refractory multiple myeloma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Myeloma
    Keywords
    Avastin, AMBER, Myeloma, Velcade

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Investigator
    Allocation
    Randomized
    Enrollment
    102 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Bortezomib + bevacizumab
    Arm Type
    Experimental
    Arm Description
    Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
    Arm Title
    Bortezomib + placebo
    Arm Type
    Active Comparator
    Arm Description
    Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.
    Intervention Type
    Drug
    Intervention Name(s)
    Bevacizumab
    Intervention Description
    15 mg/kg administered by intravenous infusion
    Intervention Type
    Drug
    Intervention Name(s)
    Bortezomib
    Intervention Description
    1.3 mg/m^2 administered by intravenous bolus injection
    Intervention Type
    Drug
    Intervention Name(s)
    placebo
    Intervention Description
    Intravenous repeating dose
    Primary Outcome Measure Information:
    Title
    Progression-free Survival (PFS)
    Description
    Progression-free survival (PFS) was defined as the time from randomization to disease progression or death on study from any cause within 30 days of the last response assessment. Disease progression was determined by the investigator using the International Myeloma Working Group's (IMWG) uniform response criteria. Median PFS was estimated using Kaplan-Meier methodology. For patients who were alive at the time of the analysis and whose disease had not yet progressed, PFS was censored at the time of the last response assessment.
    Time Frame
    From randomization to disease progression or death on study (up to 116 weeks).
    Secondary Outcome Measure Information:
    Title
    Number of Participants With an Overall Response
    Description
    Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR, respectively) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the International Myeloma Working Group's (IMWG's) uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.
    Time Frame
    From randomization to the end of study (clinical cut-off; up to 116 weeks).
    Title
    Percentage of Participants With an Overall Response
    Description
    Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the IMWG's uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.
    Time Frame
    From randomization to the end of study (clinical cut-off; up to 116 weeks).
    Title
    Duration of Response
    Description
    Duration of response was defined as the time from the initial response to disease progression or death on study. Disease progression was determined by the investigator using the IMWG's uniform response criteria and defined as an increase of ≥25% from best response in: Serum M-protein and/or Urine M-protein and/or Marrow plasma cells; or new or increased plasmacytomas or bone lesions; or hypercalcemia due to myeloma. Duration of response was estimated using Kaplan-Meier. For patients who had not progressed or died, duration of response was censored at the date of the last response assessment.
    Time Frame
    From randomization to the end of study (clinical cut-off; up to 116 weeks).
    Title
    Overall Survival (OS)
    Description
    Overall survival was defined as the duration of time from randomization until death from any cause. All deaths were included, whether they occurred on study treatment or following treatment discontinuation. Overall survival was estimated using Kaplan-Meier. For patients who had not died, overall survival was censored at the date that the patient was last known to be alive.
    Time Frame
    From randomization until death from any cause, up until the end of study (clinical cut-off; up to 116 weeks).
    Title
    Number of Participants With Selected Adverse Events (AEs)
    Description
    Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. All serious adverse events are listed in the Adverse Event Reporting section.
    Time Frame
    Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination (up to 122 weeks).

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Previously diagnosed with multiple myeloma Relapsed or refractory multiple myeloma with disease progression following one to three prior treatment regimens Measurable multiple myeloma disease Exclusion Criteria: Grade ≥ 2 peripheral neuropathy Use of corticosteroids within 21 days prior to Day 1 Use of other anti-myeloma therapy within 21 days prior to Day 1 Intolerance to bortezomib or compounds containing boron Life expectancy of < 12 weeks Current, recent, or planned participation in an experimental drug study Active malignancy other than multiple myeloma within 5 years before screening Prior treatment with bevacizumab Inadequately controlled hypertension Prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF) Decreased left ventricular function at study entry History of myocardial infarction or unstable angina within 6 months prior to Day 1 History of stroke or transient ischemic attack within 6 months prior to Day 1 Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to Day 1 Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study Core biopsy or other minor surgical procedure, including placement of a vascular access device within 7 days prior to Day 1 History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 Serious, non-healing wound, active ulcer, or untreated bone fracture (for pathologic bone fractures consistent with multiple myeloma, patients may be eligible if no treatment is planned) Albuminuria Known hypersensitivity to any component of bevacizumab Pregnancy (positive pregnancy test) or lactation
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Virginia (Ginny) Paton, M.D.
    Organizational Affiliation
    Genentech, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    A Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (AMBER)

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