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

Condition(s) targeted: Hodgkin's Disease; Non-Hodgkin's Lymphoma

Intervention: Vorinostat (SAHA) and Niacinamide (Drug); Vorinostat, Niacinamide and Etoposide (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: New York University

Official(s) and/or principal investigator(s):
Owen A O'Connor, MD, PhD, Principal Investigator, Affiliation: Columbia University

Overall contact:
Owen A O'Connor, MD, PhD, Phone: 212-305-3653

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. We 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.

Official title: Phase I Study of Vorinostat in Combination With Niacinamide, and Etoposide for the Treatment of Patients With Relapsed and Refractory Lymphoid Malignancies

Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Determine the maximum tolerated dose (MTD) of all combinations of drugs used in study as specified in protocol; evaluate the safety and toxicity of the studied combinations of vorinostat, niacinamide and etoposide

Secondary outcome:

Describe the maximum number of cycles received in each part of the study

Describe the number of dose delays and reductions at the MTD

Describe the anti-tumor activity

Evaluate pharmacodynamic markers of target effect in paired tissue biopsies

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Histologically confirmed relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's Disease (WHO criteria), for which standard curative or palliative measures do not exist or are no longer effective.

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 4 weeks (6 weeks for

nitrosoureas or mitomycin C) 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 30 days prior to the start of the study drugs.

- No monoclonal antibody within 3 months without evidence of progression

- Prior history of receiving etoposide is not a contraindication

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, if CD4 count is less than 200

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

12. Prior or concurrent therapy with any Histone Deacetylase Inhibitor, including valproic acid

Owen A O'Connor, MD, PhD, Phone: 212-305-3653

Columbia University Medical Center, NY, New York 10032, United States; Recruiting
Tasha Smith, MS, Phone: 212-305-8615, Email: ts2257@columbia.edu

NYU Cancer Institute, New York, New York 10016, United States; Not yet recruiting
Victoria Serrano, MPH, CCRP, Phone: 212-263-4415, Email: Victoria.Serrano@nyumc.org
Owen O'Connor, MD, PhD, Principal Investigator

Herbert Irving Comprehensive Cancer Center

Starting date: June 2008
Ending date: May 2013
Last updated: August 26, 2009