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