Study of Vorinostat (MK0683), an Histone Deacetylase (HDAC) Inhibitor in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (MK-0683-095)
Condition: Relapsed or Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Vorinostat; Bortezomib; Dexamethasone
Intervention description: Four 100 mg vorinostat capsules orally, once daily (QD) by mouth on Days 1-14 of each 21-day treatment cycle.; Bortezomib 1.3 mg/m^2, IV injection QD on Days 1, 4, 8, and 11 of each 21-day treatment cycle.; Five 4 mg Dexamethasone tablets orally, QD on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day treatment cycle if PD is observed after 2 treatment cycles or if NC to disease is observed after 4 treatment cycles.
Intervention MeSH terms: Dexamethasone; Bortezomib; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the clinical activity of vorinostat in combination
      with bortezomib in participants with relapsed or refractory multiple myeloma after at least 2
      prior treatment regimens. The primary objective is to define the objective response rate (RR)
      associated with the administration of vorinostat in combination with bortezomib to patients
      with relapsed and refractory multiple myeloma after at least 2 prior treatment regimens. The
      primary hypothesis of the study is the administration of vorinostat in combination with
      bortezomib will result in a clinically meaningful rate of objective response.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has an established diagnosis of multiple myeloma based on myeloma diagnostic criteria

          -  Must have adequate organ function

          -  Is refractory to prior bortezomib regimen and have also been exposed to prior
             Immunomodulatory imide drugs (IMiD: thalidimide or lenalidmide)

          -  Has relapsed and refractory multiple myeloma after at least 2 prior treatment regimens

          -  Has performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          -  Has measurable disease, defined as any quantifiable serum monoclonal (M) protein value
             and, where applicable, urine light chain of ≥200 mg/24 hours

          -  Female participants are not pregnant and not breastfeeding, and are not a woman of
             childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive
             guidance during the treatment period and for at least 30 days after the last dose of
             study intervention

          -  Male participants must agree to use approved contraception during the treatment period
             and for at least 30 days after the last dose of study intervention and refrain from
             donating sperm during this period

          -  Is relapsed, refractory, intolerant, and/or ineligible (in the opinion of the
             investigator) to other therapies including an IMiD (thalidomide or lenalidomide)

          -  Is refractory to bortezomib (no response on prior bortezomib containing regimen or
             progression on or within 60 days of bortezomib containing regimen

        Exclusion Criteria:

          -  Has known hypersensitivity to any components of bortezomib or vorinostat

          -  Has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone
             marrow transplantation within 4 weeks of the initiation of study therapy

          -  Has an active systemic infection

          -  Has acute diffuse infiltrative pulmonary disease or pericardial disease

          -  Has known hypersensitivity to any components of bortezomib or vorinostat

          -  Has active Hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus
             (HIV) positive

          -  Has 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) < 0.1; or who has undergone potentially curative
             therapy with no evidence of that disease for five years, or who is deemed at low risk
             for recurrence by his/her treating physician

          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Has plasma cell leukemia defined as the presence of more than 20% plasma cells in the
             peripheral blood and an absolute plasma cell count of at least 2000/μL

          -  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
             drug

          -  Has preexisting National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 1
             neuropathy with pain or >Grade 2 neuropathy