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Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
vorinostat
bortezomib
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

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

Inclusion Criteria: Adults with refractory or relapsed multiple myeloma Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities) Adequate bone marrow reserve Adequate hepatic and renal function Ability to swallow capsules 3 weeks or more since prior chemotherapy and have recovered from prior toxicities Exclusion Criteria: Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism Participants with other active/uncontrolled clinically significant illness Pregnant or nursing female participants Participants who received bortezomib within 3 months of start of this trial

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    vorinostat 200 mg + bortezomib 0.7 mg/m^2

    vorinostat 200 mg + bortezomib 0.9 mg/m^2

    vorinostat 300 mg + bortezomib 1.3 mg/m^2

    vorinostat 400 mg + bortezomib 0.9 mg/m^2

    vorinostat 400 mg + bortezomib 1.1 mg/m^2

    vorinostat 400 mg + bortezomib 1.3 mg/m^2

    Arm Description

    Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.

    Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.

    Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.

    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

    Outcomes

    Primary Outcome Measures

    Mean Duration of Treatment With Vorinostat
    Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity. Progressive disease was defined as: >25% increase in the level of serum monoclonal paraprotein. 25% increase in 24-hour urinary light chain excretion. >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy. Development of new bone lesions or soft tissue plasmacytomas. Development of hypercalcemia. Intolerable toxicity was based on the clinical judgment of the investigator.

    Secondary Outcome Measures

    Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug
    An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
    Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
    Clinical AE Summary
    An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.
    Laboratory AE Summary
    An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose. A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.

    Full Information

    First Posted
    May 25, 2005
    Last Updated
    May 5, 2015
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00111813
    Brief Title
    Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))
    Official Title
    Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2005 (undefined)
    Primary Completion Date
    December 2009 (Actual)
    Study Completion Date
    May 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    5. Study Description

    Brief Summary
    The purposes of this study are: To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Myeloma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    34 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    vorinostat 200 mg + bortezomib 0.7 mg/m^2
    Arm Type
    Experimental
    Arm Description
    Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
    Arm Title
    vorinostat 200 mg + bortezomib 0.9 mg/m^2
    Arm Type
    Experimental
    Arm Description
    Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
    Arm Title
    vorinostat 300 mg + bortezomib 1.3 mg/m^2
    Arm Type
    Experimental
    Arm Description
    Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Arm Title
    vorinostat 400 mg + bortezomib 0.9 mg/m^2
    Arm Type
    Experimental
    Arm Description
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Arm Title
    vorinostat 400 mg + bortezomib 1.1 mg/m^2
    Arm Type
    Experimental
    Arm Description
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Arm Title
    vorinostat 400 mg + bortezomib 1.3 mg/m^2
    Arm Type
    Experimental
    Arm Description
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Intervention Type
    Drug
    Intervention Name(s)
    vorinostat
    Other Intervention Name(s)
    MK0683, Zolinza®, Suberoylanilide Hydroxamic Acid (SAHA)
    Intervention Description
    Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).
    Intervention Type
    Drug
    Intervention Name(s)
    bortezomib
    Other Intervention Name(s)
    Velcade
    Intervention Description
    Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.
    Primary Outcome Measure Information:
    Title
    Mean Duration of Treatment With Vorinostat
    Description
    Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity. Progressive disease was defined as: >25% increase in the level of serum monoclonal paraprotein. 25% increase in 24-hour urinary light chain excretion. >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy. Development of new bone lesions or soft tissue plasmacytomas. Development of hypercalcemia. Intolerable toxicity was based on the clinical judgment of the investigator.
    Time Frame
    Day 1 to an event causing discontinuation from the study, assessed up to 29 months
    Secondary Outcome Measure Information:
    Title
    Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug
    Description
    An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
    Time Frame
    Day 1 to disease progression, toxicity, or death, assessed up to 29 months
    Title
    Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib
    Description
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
    Time Frame
    Day 1 to disease progression, toxicity, or death, assessed up to 29 months
    Title
    Clinical AE Summary
    Description
    An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.
    Time Frame
    Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)
    Title
    Laboratory AE Summary
    Description
    An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose. A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.
    Time Frame
    Day 1 up to disease progression, toxicity, or death, assessed up to 29 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Adults with refractory or relapsed multiple myeloma Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities) Adequate bone marrow reserve Adequate hepatic and renal function Ability to swallow capsules 3 weeks or more since prior chemotherapy and have recovered from prior toxicities Exclusion Criteria: Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism Participants with other active/uncontrolled clinically significant illness Pregnant or nursing female participants Participants who received bortezomib within 3 months of start of this trial
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    23040438
    Citation
    Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L, Hardwick JS, Jagannath S. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):319-24. doi: 10.1016/j.clml.2012.07.007.
    Results Reference
    derived

    Learn more about this trial

    Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))

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