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

This study is currently recruiting participants.
Verified January 2014 by Columbia University
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Owen A. O'Connor, Columbia University
ClinicalTrials.gov Identifier:
NCT00691210
First received: June 3, 2008
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hodgkin's Disease
Non-Hodgkin's Lymphoma
Drug: Vorinostat (SAHA) and Niacinamide
Drug: Vorinostat, Niacinamide and Etoposide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Vorinostat in Combination With Niacinamide, and Etoposide for the Treatment of Patients With Relapsed and Refractory Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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 [ Time Frame: continuous ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 48
Study Start Date: June 2008
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Vorinostat (SAHA) and Niacinamide
    dose escalation scheme
    Drug: Vorinostat, Niacinamide and Etoposide
    dose escalation scheme
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00691210

Locations
United States, New York
Columbia University Medical Center Recruiting
NY, New York, United States, 10022
Contact: Celeste Rojas    212-326-5720    cr2393@columbia.edu   
Principal Investigator: Owen A. O'Connor, MD, Ph.D.         
Sponsors and Collaborators
Columbia University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Owen A O'Connor, MD, Ph.D. Columbia University
  More Information

No publications provided by Columbia University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Owen A. O'Connor, Professor of Medicine and Experimental Therapeutics; Director, Center for Lymphoid Malignancies, Columbia University
ClinicalTrials.gov Identifier: NCT00691210     History of Changes
Other Study ID Numbers: AAAJ3001
Study First Received: June 3, 2008
Last Updated: January 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Hodgkin's Disease
Non-Hodgkin's Lymphoma

Additional relevant MeSH terms:
Niacinamide
Niacin
Nicotinic Acids
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide
Etoposide phosphate
Vorinostat
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on April 15, 2014