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

This study has been completed.
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: August 17, 2015
Last verified: August 2015

June 3, 2008
August 17, 2015
June 2008
February 2014   (final data collection date for primary outcome measure)
The Maximum Tolerated Dose of Niacinamide in the Combination of Vorinostat and Niacinamide [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
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 ]
Complete list of historical versions of study NCT00691210 on ClinicalTrials.gov Archive Site
  • The Greatest Number of Cycles Received in Each Treatment Group [ Time Frame: up to 45 weeks ] [ Designated as safety issue: Yes ]
    The highest number of cycles received by an individual participant in the treatment groups. Each cycle was 21 days long.
  • The Number of Dose Delays and Reductions at the MTD [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • The Prevalence of Anti-tumor Activity [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic Markers of Target Effect in Paired Tissue Biopsies [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • 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 ]
Not Provided
Not Provided
 
Phase I Vorinostat in Combination With Niacinamide and Etoposide for Lymphoid Malignancies
Phase I Study of Vorinostat in Combination With Niacinamide, and Etoposide for the Treatment of Patients With Relapsed and Refractory 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 MTD is determined.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hodgkin's Disease
  • Non-Hodgkin's Lymphoma
  • Drug: Vorinostat

    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.

    Other Name: SAHA
  • Drug: Niacinamide

    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.

    Other Name: Nicotinamide
  • Drug: Etoposide

    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."

    Other Name: VP-16
  • Experimental: V/N: Level 1
    Vorinostat: 400mg Niacinamide: 20 mg/kg rounded to 100mg
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
  • Experimental: V/N: Level 2
    Vorinostat: 400mg Niacinamide: 40 mg/kg rounded to 100mg
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
  • Experimental: V/N: Level 3
    Vorinostat: 400mg Niacinamide: 60 mg/kg rounded to 100mg
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
  • Experimental: V/N: Level 4
    Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
  • Experimental: V/N: Level 5
    Vorinostat: 400mg Niacinamide: 100 mg/kg rounded to 100mg
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
  • Experimental: V/N/E: Level 1
    Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg Etoposide: 25 mg/m2
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
    • Drug: Etoposide
  • Experimental: V/N/E: Level 2
    Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg Etoposide: 50 mg/m2
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
    • Drug: Etoposide
  • Experimental: V/N/E: Level 3
    Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg Etoposide: 100 mg/m2
    Interventions:
    • Drug: Vorinostat
    • Drug: Niacinamide
    • Drug: Etoposide
Amengual JE, Clark-Garvey S, Kalac M, Scotto L, Marchi E, Neylon E, Johannet P, Wei Y, Zain J, O'Connor OA. Sirtuin and pan-class I/II deacetylase (DAC) inhibition is synergistic in preclinical models and clinical studies of lymphoma. Blood. 2013 Sep 19;122(12):2104-13. doi: 10.1182/blood-2013-02-485441. Epub 2013 Aug 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
38
March 2015
February 2014   (final data collection date for primary outcome measure)

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 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00691210
AAAJ3001
Yes
Owen A. O'Connor, Columbia University
Columbia University
Merck Sharp & Dohme Corp.
Principal Investigator: Owen A O'Connor, MD, Ph.D. Columbia University
Columbia University
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP