Ignite Creation Date:
2024-05-05 @ 7:59 PM
Last Modification Date:
2024-10-26 @ 9:56 AM
Study NCT ID:
NCT00773747
Status:
COMPLETED
Last Update Posted:
2021-04-30
First Post:
2008-10-14
Brief Title:
Study of Vorinostat MK-0683 or Placebo in Combination With Bortezomib in Participants With Multiple Myeloma MK-0683-088 AMN
Sponsor:
Merck Sharp Dohme LLC
Organization:
Merck Sharp Dohme LLC
Study Overview
Official Title:
An International Multicenter Randomized Double-Blind Study of Vorinostat MK-0683 or Placebo in Combination With Bortezomib in Patients With Multiple Myeloma
Status:
COMPLETED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 3Induction of ER stress signal and 4 acetylation of Dyneindisruption of aggresome functionformation 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 2045 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2008-003752-30 | EUDRACT_NUMBER | Merck Protocol Number | None |
| MK-0683-088 | OTHER | None | None |