Study of Vorinostat (MK-0683) an HDAC Inhibitor, or Placebo in Combination With Bortezomib in Patients With Multiple Myeloma (MK-0683-088 AMN)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00773747
First received: October 14, 2008
Last updated: September 3, 2014
Last verified: September 2014

October 14, 2008
September 3, 2014
December 2008
September 2011   (final data collection date for primary outcome measure)
Duration of progression-free survival (PFS) in participants treated with vorinostat + bortezomib versus placebo + bortezomib [ Time Frame: From randomization to event of disease progression or death ] [ Designated as safety issue: No ]
Determine the TTP (time-to-progression) in patients with multiple myeloma, treated with bortezomib and vorinostat compared to patients treated with bortezomib and placebo [ Time Frame: 33 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00773747 on ClinicalTrials.gov Archive Site
  • Number of participants with clinical and laboratory adverse events (AEs). [ Time Frame: From first dose to 30 days after last dose of study drugs ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: From randomization to up to 2 years post last dose in participants treated with vorinostat + bortezomib versus placebo + bortezomib ] [ Designated as safety issue: No ]
  • Time to tumor progression (TTP) in participants treated with vorinostat + bortezomib versus placebo + bortezomib [ Time Frame: Every 21 days ] [ Designated as safety issue: No ]
  • Overall response rate (ORR) in participants treated with vorinostat + bortezomib versus placebo + bortezomib [ Time Frame: Every 21 days ] [ Designated as safety issue: No ]
Assess the tolerability of vorinostat administered in combination with bortezomib. [ Time Frame: 33 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of Vorinostat (MK-0683) an HDAC Inhibitor, or Placebo in Combination With Bortezomib in Patients With Multiple Myeloma (MK-0683-088 AMN)
An International, Multicenter, Randomized, Double-Blind Study of Vorinostat (MK0683) or Placebo in Combination With Bortezomib in Patients With Multiple Myeloma

Study of the efficacy and safety of bortezomib administered in combination with vorinostat in patients with relapsed or refractory multiple myeloma. Histone deacetylases (HDAC) facilitate gene transcription by modulating the uncoiling of chromatin. HDAC function is dysregulated in hematologic and solid malignancies, and this dysregulation may result in over-expression of oncogenes. Thus, inhibition of HDACs may result in anti-cancer effects. HDAC inhibitors, like vorinostat, represent a new class of antitumor agents that have the ability to induce antiproliferative effects including cyto-differentiation, cell cycle growth arrest or apoptosis in various cancer cell lines. Several studies have investigated the in vitro antimyeloma activity of vorinostat in combination with bortezomib and have demonstrated that vorinostat may act synergistically with bortezomib to modulate tumor cell growth. Mitsiades et al have shown that vorinostat enhances the sensitivity of bortezomib. Pei et al found that exposure of human multiple myeloma cell lines & patient-derived multiple myeloma cells to bortezomib and vorinostat resulted in synergistic interactions as a result of: (1) Interruption of NF-kB & related signaling pathways (JNK, XIAP, Mcl-1, etc.) (2) Inhibition of Hsp90 (3)Induction of ER stress signal and (4) acetylation of Dynein/disruption of aggresome function/formation, salvage for ubiquitinated proteins. In addition a marked increase in mitochondrial injury, caspase activation, and apoptosis was also observed. Bortezomib is indicated for the treatment of patients with multiple myeloma. Two Phase I dose-ranging studies of a regimen combining vorinostat and bortezomib among patients with relapsed as well asend-stage, refractory multiple myeloma have been conducted. These studies enrolled a total of 57 patients. In these studies, administration of vorinostat with standard doses of bortezomib resulted in responses in 20/45 (44%) evaluable patients (Weber et al 2007, Badros et al 2007). The purpose of the present study is to definitively evaluate the clinical activity of vorinostat in combination with bortezomib inpatients with multiple myeloma.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: vorinostat
    Four 100 mg capsules vorinostat taken orally, once daily, on Days 1-14 of each 21-day treatment cycle.
    Other Name: Zolinza
  • Drug: bortezomib
    1.3 mg/m2 of bortezomib by IV push, on Days 1, 4, 8, and 11 of each 21-day treatment cycle.
    Other Name: Velcade
  • Drug: placebo to vorinostat
    Four placebo capsules taken orally, once daily, on Days 1-14 of each 21-day treatment cycle.
  • Experimental: Vorinostat + bortezomib arm
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Placebo Comparator: Placebo + bortezomib arm
    Interventions:
    • Drug: bortezomib
    • Drug: placebo to vorinostat
Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-40. doi: 10.1016/S1470-2045(13)70398-X. Epub 2013 Sep 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
637
March 2015
September 2011   (final data collection date for primary outcome measure)

Inclusion criteria

  • Participant has an established diagnosis of multiple myeloma based on the myeloma diagnostic criteria.
  • Participant has received at least 1 but not more than 3 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen.
  • Participant must have adequate organ function.

Exclusion criteria:

  • Participant has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation within 4 weeks of the initiation of study therapy.
  • Participant has known hypersensitivity to any components of bortezomib or vorinostat.
  • Participant has active Hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive.
  • Participant has had prior treatment with vorinostat or histone deacetylase (HDAC) inhibitors.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00773747
0683-088, 2008_525
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
September 2014

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