Phase I Vorinostat in Combination With Niacinamide and Etoposide for Lymphoid Malignancies
Condition: Hodgkin's Disease; Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma, Non-Hodgkin; Hodgkin Disease
Intervention: Vorinostat; Niacinamide; Etoposide
Intervention description: Dose escalation scheme (400 mg)
Vorinostat is used to treat cutaneous T-cell lymphoma (CTCL, a type of cancer) in people whose disease has not improved, has gotten worse, or has come back after taking other medications. Vorinostat is in a class of medications called histone deacetylase (HDAC) inhibitors. It works by killing or stopping the growth of cancer cells.; Dose escalation scheme (20, 40, 60, 80, 100 mg/kg rounded to 100 mg)
Niacinamide is a water soluble B-vitamin that has been evaluated for use in the treatment of pellagra, bullous pemphigoid, and as a radiation sensitizer in head and neck cancer.; Dose escalation scheme (0, 25, 50, 100 mg/m2)
Etoposide is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. This medication is classified as a "plant alkaloid" and "topoisomerase II inhibitor."
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids; Etoposide; Vorinostat
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hodgkin's Disease; Non-Hodgkin's Lymphoma

Summary:

      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.
    

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