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

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ClinicalTrials.gov Identifier: NCT00111813
Recruitment Status : Completed
First Posted : May 26, 2005
Results First Posted : April 6, 2011
Last Update Posted : May 21, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 25, 2005
First Posted Date  ICMJE May 26, 2005
Results First Submitted Date  ICMJE March 10, 2011
Results First Posted Date  ICMJE April 6, 2011
Last Update Posted Date May 21, 2015
Study Start Date  ICMJE September 2005
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2015)
Mean Duration of Treatment With Vorinostat [ Time Frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00111813 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2011)
  • Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug [ Time Frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months ]
    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 [ Time Frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months ]
    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 [ Time Frame: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months) ]
    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 [ Time Frame: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))
Official Title  ICMJE Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: vorinostat
    Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).
    Other Names:
    • MK0683
    • Zolinza®
    • Suberoylanilide Hydroxamic Acid (SAHA)
  • Drug: bortezomib
    Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.
    Other Name: Velcade
Study Arms  ICMJE
  • Experimental: vorinostat 200 mg + bortezomib 0.7 mg/m^2
    Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 200 mg + bortezomib 0.9 mg/m^2
    Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 300 mg + bortezomib 1.3 mg/m^2
    Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 400 mg + bortezomib 0.9 mg/m^2
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 400 mg + bortezomib 1.1 mg/m^2
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 400 mg + bortezomib 1.3 mg/m^2
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 27, 2010)
34
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2011
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00111813
Other Study ID Numbers  ICMJE 0683-015
2005_018
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP