Relapsed and/or Refractory Non-Hodgkin Lymphoma Study

• Histologically confirmed non-Hodgkin Lymphoma including small lymphocytic lymphoma, lymphoplasmacytic lymphoma, follicular center cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma, anaplastic large cell lymphoma, nasal NK/T cell lymphoma, mycosis fungoides/Sezary syndrome, angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphomas not otherwise specified
• Received 2 or > prior therapies, which may include hematopoietic cell transplant (HCT)
• Received treatment with a nucleoside analog, or an alkylating agent, an anthracycline and/or in the case of B cell lymphomas, rituximab
• Resistant disease to 2 regimens or resistant disease to at least 1 regimen after first relapse

• Bi-dimensionally measurable disease documented within 30 days prior to enrollment. Bidimensionally measurable disease is defined as:

  • A lymph node or tumor mass that can be accurately measured in two dimensions by CT,MRI, medical photograph (skin or oral lesion), plain X-ray, PET scan or other conventional technique and a greatest diameter of 1 cm or >; or palpable lesions with both diameters > 2 cm (lesion measured in 2 largest perpendicular dimensions in millimeters)
  • For the purposes of this protocol, disease should be located in an area of no prior radiation therapy or a clear progression in an area that was previously irradiated

• Adequate organ and marrow function obtained \< or = to 14 days prior to enrollment as defined by a(n):

  • ANC > or = to 1,000/microliter
  • Platelet count > or = to 100,000/microliter, or > or = to 75,000/microliter if the bone marrow is involved
  • Hemoglobin level > or = to 9 g/dL
  • Total bilirubin \< or = to 1.5 x institutional upper limit of normality (ULN).(If abnormal, direct bilirubin less than or equal to 1.5 x institutional ULN)
  • ALT or AST \< or = to 2.5 x institutional ULN (\< or = to 5 x institutional ULN if liver involvement with lymphoma)
  • Serum creatinine \< or = to 1.5 x institutional ULN
• Zubrod (ECOG) Performance Status of 0 or 1
• Age > than or = to 18 years
• Life expectancy > or = to 3 months as clinically determined by referring physician
• Female patient is either post menopausal, free from menses for > 2 years, surgically sterilized or willing to use highly effective methods of contraception (i.e., a condom in conjunction with a diaphragm, or spermicidal jelly; or oral, injectable, or implanted birth control; or abstinence ) to prevent pregnancy throughout the study, starting with visit 1
• Female patients of childbearing potential must have a negative serum pregnancy test (beta-HCG) within 72 hours of enrollment and should not be nursing due to the potential for congenital abnormalities and of harm to nursing infants due to this treatment regimen
• Male patient agrees to use an adequate method of contraception (i.e., a condom if female partner uses a diaphragm, spermicidal jelly; or oral, injectable, or implanted birth control; or abstinence) for the duration of the study and for 12 weeks after the last dose
• Patient must be able to swallow capsules
• Signed and dated IRB/ethics committee-approved informed consent before any protocol specific screening procedures are performed
• Both men and women of all races and ethnic groups are eligible for this trial

Exclusion Criteria:

• Prior investigational therapy within 3 weeks of enrollment. Investigational therapy is defined as treatment that is not approved for any indication
• CNS metastases, as indicated by clinical symptoms,cerebral edema, requirement for corticosteroids and/or progressive growth (treated CNS metastases must be stable for greater than 2 weeks prior to enrollment)
• Active second malignancy that requires treatment or that would interfere with assessment of response
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer with \< 5 years of documented disease-free status

• Treatment with the following within the timeframe specified prior to enrollment:

  • Chemotherapy, radiotherapy, immunotherapy (active (such as vaccines) or passive (such as monoclonal antibodies or immunotoxins)) or major surgery \< or = to 3 weeks;
  • Nitrosourea, or mitomycin \< or = to 6 weeks
  • Radioimmunotherapy (e.g. Bexxar or Zevalin) \< or = to 12 weeks
  • Concurrent enzyme-inducing anticonvulsant agents or valproic acid in last 4 weeks
  • Prior bortezomib or any other proteasome inhibitor
  • Prior vorinostat or any other histone deacetylase inhibitor
  • Concurrent systemic corticosteroids (\<10 mg/day of prednisone or equivalent for adrenal insufficiency or acute allergic reactions allowed)

• Uncontrolled current illness including, but not limited to:

  • Clinically or laboratory determined active infection
  • Clinically limiting congestive heart failure or ejection fraction (EF) \<45%
  • Clinically unstable angina pectoris (or myocardial infarction within 6 months of Day 1)
  • Clinically significant cardiac arrhythmia
  • Limiting pulmonary hypertension
  • Pre-existing neuropathy ≥ grade 2
  • Patients with pleural effusions, ascites or peripheral edema grade 2 or >
• HIV
• Active viral hepatitis
• Major surgery or significant traumatic injury within 21 days prior to enrollment (this does not apply to placement of a venous access device)
• Hypersensitivity to any of the components in vorinostat or bortezomib or agents containing boron or mannitol
• Significant psychiatric illness/social situations that would limit compliance with study medication and requirements of the study as determined by study MD
• Significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study