This phase II trial is studying how well vorinostat works in treating patients with relapsed or refractory advanced Hodgkin's lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the response probability (complete, complete unconfirmed, and partial) in patients with relapsed or refractory Hodgkin's lymphoma.

II. To estimate 1-year progression-free survival and overall survival in patients with relapsed or refractory Hodgkin's lymphoma treated with SAHA.

III. To assess the toxicity profile of SAHA in this patient population. IV. To perform gene expression profiling on tumor tissue before and after treatment in order to explore in a preliminary manner the association between response and specific gene expression results.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of therapy beyond CR.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed relapsed/refractory Hodgkin's lymphoma of any subtype; patients with lymphocyte predominant Hodgkin's disease (LPHD) are also eligible; clear evidence of disease progression or lack of response after the most recent therapy, including local radiation is required
• Patients must be willing to submit specimens for correlative studies
• All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
• Patients must have unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
• Patients may have had up to five prior chemotherapy regimens
• Patients must have completed chemotherapy at least 28 days prior to registration and all toxicities must have resolved (in the opinion of the treating investigator); if last regimen included nitrosoureas or mitomycin then 42 days must have elapsed since completion of treatment; patients must not have taken valproic acid, or another histone deacetylase inhibitor, for at least 14 days prior to registration
• Patients must have completed all radiotherapy at least 14 days prior to registration and all toxicities must have resolved (in the opinion of the treating investigator)
• Patients who relapse after autologous stem cell transplant may be enrolled if they are at least three months after transplant, and after allogeneic transplant if they are at least one year posttransplant; patients should have no active related infections (i.e., fungal or viral); in the case of allogeneic transplant relapse, there should be no active acute graft versus host disease (GvHD) of any grade, and no chronic graft versus host disease other than mild skin, oral, or ocular GvHD not requiring systemic immunosuppression
• Patients must have a Zubrod performance status of 0-2
• Patients must have a CT scan of the chest/abdomen and pelvis performed within 28 days prior to registration
• Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration
• Serum LDH must be measured within 28 days prior to registration
• Absolute neutrophil count >- 1,000/mcL
• Platelet count >= 100,000/mcL
• SGOT/SGPT < 2.5 x the institutional upper limit of normal
• Serum creatinine < 2 x the institutional upper limit of normal
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biological composition to SAHA are ineligible
• Patients must not have plans to receive concurrent hormonal, biological or radiation therapy; patients with potentially curative options such as salvage therapy with chemotherapy or hematopoietic stem cell transplant (HSCT) are not eligible
• Patients with a history of prior myocardial infarction, unstable angina, or stroke within 6 months are ineligible
• Patients known to be HIV-positive and receiving combination antiretroviral therapy are ineligible; in addition, HIV-positive patients not receiving combination antiretroviral therapy are also ineligible
• No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for five years
• Pregnant or nursing women may not participate; women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines