Vorinostat, Bortezomib, and Doxorubicin Hydrochloride Liposome in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT00744354

Last Updated: 2018-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2015-04-30

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non-Randomized Open Label Single Arm

Phase 1 dose escalation trial of vorinostat in combination with bortezomib and pegylated liposomal doxorubicin hydrochloride.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Intravenous Push 1.3 mg/m2 Days 1, 4, 8, and 11

pegylated liposomal doxorubicin hydrochloride

Intervention Type: DRUG

Intravenous infusion, 30mg/m2, Day 4, each cycle

vorinostat

Intervention Type: DRUG

Oral, 300mg, Days 1, 2, 4, 5, 8, 9, 11, 12, every cycle.

Interventions

bortezomib

Intravenous Push 1.3 mg/m2 Days 1, 4, 8, and 11

Intervention Type: DRUG

pegylated liposomal doxorubicin hydrochloride

Intravenous infusion, 30mg/m2, Day 4, each cycle

Intervention Type: DRUG

vorinostat

Oral, 300mg, Days 1, 2, 4, 5, 8, 9, 11, 12, every cycle.

Intervention Type: DRUG

Other Intervention Names

Velcade; Doxil; Zolinza

Eligibility Criteria

Exclusion Criteria

• Patients must have adequate cardiovascular function, defined by all of the following:

• No EKG evidence of active, clinically significant conduction system abnormalities
• No EKG evidence of QTc prolongation > grade 2
• NOTE: Any EKG abnormality at screening has to be documented by the investigator as not medically significant.

PRIOR CONCURRENT THERAPY:

• No limit to number of prior treatment regimens
• At least 30 days since prior therapy and recovered
• At least 3 months since prior autologous stem cell transplantation and recovered
• Prior allogeneic stem cell or bone marrow transplantation allowed provided the following criteria are met:

• More than 1 year since transplantation
• No longer receiving immunosuppressive therapy or treatment for graft-versus-host disease (GVHD) prophylaxis
• No active GVHD
• No active, uncontrolled infections
• No major surgery within the past 3 weeks
• No prior anthracycline dose > 360 mg/m^2 for doxorubicin hydrochloride (including pegylated liposomal doxorubicin hydrochloride [PLD]) or 720 mg/m^2 for epirubicin hydrochloride
• No prior or concurrent histone deacetylase inhibitor (e.g., valproic acid)
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during course 1
• No other concurrent investigational or anticancer agent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Ortho Biotech, Inc.

INDUSTRY

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brandi Reeves, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Mount Sinai Medical Center

New York, New York, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

Related Links

http://unclineberger.org

Web address for UNC Lineberger Comprehensive Cancer Center

Other Identifiers

08-1073

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 0715

Identifier Type: -

Identifier Source: org_study_id