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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00744354
First received: August 29, 2008
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: pegylated liposomal doxorubicin hydrochloride
Drug: vorinostat
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of vorinostat [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: October 2008
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: bortezomib
    Intravenous Push 1.3 mg/m2 Days 1, 4, 8, and 11
    Other Name: Velcade
    Drug: pegylated liposomal doxorubicin hydrochloride
    Intravenous infusion, 30mg/m2, Day 4, each cycle
    Other Name: Doxil
    Drug: vorinostat
    Oral, 300mg, Days 1, 2, 4, 5, 8, 9, 11, 12, every cycle.
    Other Name: Zolinza
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Relapsed or refractory disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • ANC ≥ 1.0 x 10^9/L (no granulocyte growth factor support, e.g., G-CSF or GM-CSF allowed)
  • Platelet count ≥ 100 x 10^9/L (erythropoietin allowed, no platelet or RBC transfusion within the past 2 weeks)
  • Hemoglobin ≥ 8 g/dL (erythropoietin allowed, no platelet or RBC transfusion within the past 2 weeks)
  • Creatinine clearance ≥ 30 mL/min
  • AST or ALT ≤ 2.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • LVEF ≥ 45% by MUGA or ECHO
  • Symptomatic neuropathy < grade 2
  • No known history of HIV
  • No active or serious infection, medical or psychiatric illness that would preclude study participation
  • No active hepatitis B or C infection
  • No other prior or concurrent malignancy except for adequately treated basal cell or squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate cancer after curative therapy, or other cancer for which the patient has been disease-free for ≥ 3 years
  • No history of hypersensitivity reaction to bortezomib or any of its components (boron, mannitol), vorinostat, doxorubicin hydrochloride, or any of the components of PLD
  • No serum potassium ≤ 3.0 or serum magnesium ≤ 1.6 that cannot be corrected with supplementation are excluded
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00744354

Locations
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
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Peter Voorhees, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00744354     History of Changes
Other Study ID Numbers: LCCC 0715, P30CA016086, CDR0000612431, ORTHO-UNC-LCCC0715, 08-1073
Study First Received: August 29, 2008
Last Updated: June 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Vorinostat
Bortezomib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014