A Study to Evaluate the Use of the Drug Combination Vorinostat, Niacinamide, and Etoposide in Patients With Lymphoid Malignancies That Have Reoccurred (SAHA)

• Describe the maximum number of cycles received in each part of the study [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
• Describe the number of dose delays and reductions at the MTD [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
• Describe the anti-tumor activity [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
• Evaluate pharmacodynamic markers of target effect in paired tissue biopsies [ Time Frame: continuous ] [ Designated as safety issue: Yes ]

The purpose of this study is to test the safety of a combination of two anticancer medicines, called vorinostat and etoposide, with a high dose of a vitamin called niacinamide. These medications will be tested at different dose levels. The investigators want to find out what effects, good and/or bad, it has on patients and their recurrent lymphoma. The first two drugs, vorinostat and niacinamide, suppress survival signals that lymphoma cells depend on. The third drug, etoposide can kill sensitive lymphoma cells alone or in combination with other chemotherapy drugs.Vorinostat is an anticancer agent that been approved by the Food and Drug Administration for use in cutaneous Tcell lymphoma. It is being evaluated in this study in combination with other anticancer medicines for use in other types of lymphoma. Vorinostat's use in combination with anticancer regimens is experimental. Niacinamide is a vitamin that is investigational or experimental when given at high doses as an anticancer agent. Niacinamide has not yet been approved by the Food and Drug Administration for use in lymphoma. Etoposide has been approved by the Food and Drug Administration for use in aggressive nonHodgkin's lymphoma. However, the way it will be given in this clinical study is experimental.

• Hodgkin's Disease
• Non-Hodgkin's Lymphoma

• Drug: Vorinostat (SAHA) and Niacinamide
  dose escalation scheme
• Drug: Vorinostat, Niacinamide and Etoposide
  dose escalation scheme

Inclusion Criteria:

1. Histologically confirmed relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's Disease (WHO criteria), for which they are unwilling or unable to undergo an autologous stem cell transplant
2. Must have received first line chemotherapy. No upper limit to number of prior therapies
3. Evaluable Disease
4. Age >18 years
5. ECOG performance status <2
6. Life expectancy of greater than 3 months
7. Patients must have adequate organ and marrow function
8. Adequate Contraception
9. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Prior Therapy

   • Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
   • Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone during the 7 days prior to the start of the study drugs
   • No monoclonal antibody within 3 months without evidence of progression
2. Patients may not be receiving any other investigational agents
3. Patients with known central nervous system metastases, including lymphomatous meningitis
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat, niacinamide or etoposide
5. Uncontrolled intercurrent illness
6. Pregnant women
7. Nursing women
8. Patient with a history of a prior malignancy
9. Patient is known to be Human Immunodeficiency Virus (HIV)-positive
10. Active Hepatitis A, Hepatitis B, or Hepatitis C infection
11. Patient has a history of surgery that would interfere with the administration or absorption of the oral study drugs