Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant
Condition: DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib; Vorinostat
Intervention description: Given IV; Given PO
Intervention MeSH terms: Bortezomib; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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/mm^3 and absolute granulocyte
             count > 1500 cells/mm^3 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