Vorinostat, Bortezomib, and Doxorubicin Hydrochloride Liposome in Treating Patients With Relapsed or Refractory Multiple Myeloma
RATIONALE: Vorinostat and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of multiple myeloma by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving doxorubicin hydrochloride liposome together with vorinostat and bortezomib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and to see how well it works when given together with bortezomib and doxorubicin hydrochloride liposome in treating patients with relapsed or refractory multiple myeloma.
Multiple Myeloma and Plasma Cell Neoplasm
Drug: pegylated liposomal doxorubicin hydrochloride
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1 Dose Escalation Study of Bortezomib (Velcade®), Pegylated Liposomal Doxorubicin (Doxil®), and Vorinostat (Suberoylanilide Hydromaxic Acid, Saha, Zolinzatm) in Patients With Relapse/Refractory Multiple Myeloma|
- Maximum tolerated dose of vorinostat [ Time Frame: 4 years ]
- Overall response rate [ Time Frame: 5 years ]
- Duration of response [ Time Frame: 5 years ]
|Study Start Date:||October 2008|
|Study Completion Date:||April 2015|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Non-Randomized Open Label Single Arm
Phase 1 dose escalation trial of vorinostat in combination with bortezomib and pegylated liposomal doxorubicin hydrochloride.
Intravenous Push 1.3 mg/m2 Days 1, 4, 8, and 11
Other Name: VelcadeDrug: pegylated liposomal doxorubicin hydrochloride
Intravenous infusion, 30mg/m2, Day 4, each cycle
Other Name: DoxilDrug: vorinostat
Oral, 300mg, Days 1, 2, 4, 5, 8, 9, 11, 12, every cycle.
Other Name: Zolinza
- To determine the maximum tolerated dose of vorinostat when added to the standard regimen of bortezomib and pegylated liposomal doxorubicin hydrochloride in patients with relapsed or refractory multiple myeloma.
- To identify the dose-limiting toxicities of this regimen in these patients.
- To gain preliminary evidence of antitumor activity of this regimen in these patients.
- To assess the degree of proteasome inhibition achieved with this regimen in these patients.
- To evaluate the accumulation of acetylated alpha-tubulin after treatment with vorinostat.
- To evaluate overall survival, time to progression, and progression-free survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose escalation study of vorinostat.
Patients receive oral vorinostat once daily on days 1,2; 4,5; 8, 9; 11, 12; bortezomib IV on days 1, 4, 8, and 11, and pegylated liposomal doxorubicin hydrochloride IV on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for proteasome inhibition assays and acetylated alpha-tubulin studies.
After completion of study treatment, patients are followed at 1 and 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00744354
|United States, New York|
|Mount Sinai Medical Center|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|Principal Investigator:||Peter Voorhees, MD||UNC Lineberger Comprehensive Cancer Center|