Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00839956
Collaborator
National Cancer Institute (NCI) (NIH)
31
1
1
97.9
0.3

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects of giving bortezomib together with vorinostat and to see how well it works in treating patients with multiple myeloma who have undergone autologous stem cell transplant. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat after an autologous stem cell transplant may stop the growth of any cancer cells that remain after transplant.

Detailed Description

PRIMARY OBJECTIVES:
  1. Evaluate the toxicity of the use of vorinostat and bortezomib as maintenance therapy after autologous transplant.
SECONDARY OBJECTIVES:
  1. Evaluate the median time to disease progression.

  2. Evaluate survival.

OUTLINE: Patients receive bortezomib intravenously (IV) on days 2 and 5 and vorinostat orally (PO) once daily (QD) on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant for Multiple Myeloma
Study Start Date :
Feb 1, 2009
Actual Primary Completion Date :
Aug 1, 2012
Actual Study Completion Date :
Mar 31, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (enzyme inhibitor therapy)

Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib
Given IV
Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade
  • Drug: Vorinostat
    Given PO
    Other Names:
  • L-001079038
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza
  • Outcome Measures

    Primary Outcome Measures

    1. Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [The first three months of therapy]

      The first three months of therapy will be used as the time period in which toxicity will be evaluated and stopping rules for unacceptable toxicity will be implemented. Rules for stopping the study will be based on the rate of withdrawal due to significant toxicity (grade IV, non-hematological, non-metabolic, nonperipheral neuropathy).

    Secondary Outcome Measures

    1. Time to Disease Progression in Patients Who Progressed [Up to 5 years]

      Patients will be followed for initial response to therapy and for progression of disease. Response criteria will be scored according to International Myeloma Working Group uniform response criteria.

    2. Survival for All Patients [Up to 5 years]

    3. Median Follow-up Survival for All Patients [Up to 5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2) therapy or peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial whose primary endpoint is also evaluating long-term, disease-free survival, or survival

    • Platelet count (transfusion independent) > 75,000 cells/mm3 and absolute granulocyte count > 1500 cells/mm3 for 5 calendar days after recovery from high dose therapy

    • Consenting for study between 30 days to 120 days after transplant

    • Female patient of childbearing potential has a negative serum pregnancy test beta-hCG within 72 hours prior to receiving the first dose of vorinostat

    • Female patient is either post-menopausal, free from menses for >= 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the treatment on study, starting with visit 1 and for 3 months afterward

    • Male patient agrees to use an adequate method of contraception for the duration of the treatment on study and for 3 months afterward

    Exclusion Criteria:
    • Eastern Cooperative Oncology Group (ECOG) performance status >= 2

    • A left ventricular ejection fraction less than 45% pre-transplant

    • Congestive heart disease with transplant, history of myocardial infarction (MI), history of coronary artery disease, or prolonged corrected QT interval (QTC)

    • Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease)

    • Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2.5 x upper limit of normal (ULN)

    • Creatinine clearance < 20 ml/minute, calculated by Cockroft-Gault formula or measured urine

    • Cannot give informed consent

    • Untreated systemic infection

    • Poorly-controlled diabetes mellitus (DM)

    • = grade 3 peripheral neuropathy

    • Prior history of human immunodeficiency virus (HIV) positivity with pre-transplant evaluation or known history of hepatitis B or C

    • Previous history of hypersensitivity to Bortezomib, boron, or mannitol; known hypersensitivity to the components of study drug or its analogs

    • Require therapeutic anticoagulation treatment, especially with coumadin

    • Potassium (K) and magnesium (Mg) < normal limits

    • Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s) or who has not recovered from adverse events due to agents administered more than 30 days earlier; patients who have received localized consolidation radiation to bone only less than 30 days prior to study entry are allowed

    • Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drugs

    • Patient had prior treatment with an histone deacetylase inhibitor (HDAC) inhibitor (e.g., romidespin [depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc.)

    • Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study

    • Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period

    • History of central nervous system (CNS) disease

    • Symptomatic ascites or pleural effusions

    • Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

    • Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse

    • Patient is pregnant or breast-feeding, or expecting to conceive or father children within the projected duration of the study

    • Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of disease for five years, and/or who is deemed at low risk for recurrence by his/her treating physician

    • Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate

    • Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Leona Holmberg, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00839956
    Other Study ID Numbers:
    • 2253.00
    • NCI-2009-01474
    • 2253
    • 2253.00
    • P30CA015704
    First Posted:
    Feb 10, 2009
    Last Update Posted:
    May 9, 2017
    Last Verified:
    Apr 1, 2017

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    Period Title: Overall Study
    STARTED 31
    COMPLETED 19
    NOT COMPLETED 12

    Baseline Characteristics

    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    Overall Participants 31
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    22
    71%
    >=65 years
    9
    29%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    60
    Sex: Female, Male (Count of Participants)
    Female
    19
    61.3%
    Male
    12
    38.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    31
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    4
    12.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    3.2%
    White
    26
    83.9%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    31
    100%

    Outcome Measures

    1. Primary Outcome
    Title Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
    Description The first three months of therapy will be used as the time period in which toxicity will be evaluated and stopping rules for unacceptable toxicity will be implemented. Rules for stopping the study will be based on the rate of withdrawal due to significant toxicity (grade IV, non-hematological, non-metabolic, nonperipheral neuropathy).
    Time Frame The first three months of therapy

    Outcome Measure Data

    Analysis Population Description
    No patients met stopping rules for significant toxicity in the first three months of therapy.
    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    Measure Participants 31
    Count of Participants [Participants]
    0
    0%
    2. Secondary Outcome
    Title Time to Disease Progression in Patients Who Progressed
    Description Patients will be followed for initial response to therapy and for progression of disease. Response criteria will be scored according to International Myeloma Working Group uniform response criteria.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    One subject withdrew from the study within first week of study therapy and changed to different therapy and is not included in this outcome measure.
    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    Measure Participants 30
    Median (Full Range) [years]
    2.1
    3. Secondary Outcome
    Title Survival for All Patients
    Description
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    Measure Participants 30
    Count of Participants [Participants]
    25
    80.6%
    4. Secondary Outcome
    Title Median Follow-up Survival for All Patients
    Description
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    Measure Participants 30
    Median (Full Range) [years]
    5.15

    Adverse Events

    Time Frame Any adverse event that occurs within 30 days of study treatment
    Adverse Event Reporting Description Adverse events grades 3 or higher evaluated.
    Arm/Group Title Arm I (Bortezomib and Vorinostat)
    Arm/Group Description Patients receive bortezomib IV on days 2 and 5 and vorinostat PO QD on days 1-14. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Vorinostat: Given PO
    All Cause Mortality
    Arm I (Bortezomib and Vorinostat)
    Affected / at Risk (%) # Events
    Total 0/31 (0%)
    Serious Adverse Events
    Arm I (Bortezomib and Vorinostat)
    Affected / at Risk (%) # Events
    Total 3/31 (9.7%)
    Immune system disorders
    Anaphylactic reaction 1/31 (3.2%)
    Infections and infestations
    Influenza A Infection 1/31 (3.2%)
    Investigations
    Elevated Creatinine Kinase Levels 1/31 (3.2%)
    Other (Not Including Serious) Adverse Events
    Arm I (Bortezomib and Vorinostat)
    Affected / at Risk (%) # Events
    Total 21/30 (70%)
    Gastrointestinal disorders
    Diarrhea 2/30 (6.7%)
    Nausea 2/30 (6.7%)
    General disorders
    Fatigue 4/30 (13.3%)
    Investigations
    Neutrophil count decreased 9/30 (30%)
    Platelet count decreased 4/30 (13.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Leona A. Holmberg
    Organization Fred Hutchinson Cancer Research Center
    Phone 206-667-6447
    Email lholmber@fredhutch.org
    Responsible Party:
    Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00839956
    Other Study ID Numbers:
    • 2253.00
    • NCI-2009-01474
    • 2253
    • 2253.00
    • P30CA015704
    First Posted:
    Feb 10, 2009
    Last Update Posted:
    May 9, 2017
    Last Verified:
    Apr 1, 2017