Phase I Vorinostat in Combination With Niacinamide and Etoposide for Lymphoid Malignancies

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 T-cell 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 non-Hodgkin's lymphoma. However, the way it will be given in this clinical study is experimental.

Subjects will be treated with vorinostat administered orally with daily dosing for 14 days of a 21-day treatment cycle in combination with niacinamide administered orally for 14 days in 21-day treatment cycle and etoposide administered intravenously on days 8,9 and 10 of a 21-day treatment cycle. Etoposide dose will be escalated until maximum tolerated dose (MTD) is determined.

Eligibility Criteria:
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. Eastern Cooperative Oncology Group (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 unless 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. Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3 years
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