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

NCT00691210 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAJ3001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hodgkin's Disease; Non-Hodgkin's Lymphoma

Keywords

Hodgkin's Disease; Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose (MTD) of Niacinamide in the Combination of Vorinostat and Niacinamide

  3 years

Secondary Outcomes (4)

• The Greatest Number of Cycles Received in Each Treatment Group

  up to 45 weeks

• The Number of Dose Delays and Reductions at the MTD

  continuous

• The Prevalence of Anti-tumor Activity

  continuous

• Pharmacodynamic Markers of Target Effect in Paired Tissue Biopsies

  continuous

Study Arms (8)

V/N: Level 1

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 20 mg/kg rounded to 100mg

Drug: Vorinostat; Drug: Niacinamide

V/N: Level 2

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 40 mg/kg rounded to 100mg

Drug: Vorinostat; Drug: Niacinamide

V/N: Level 3

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 60 mg/kg rounded to 100mg

Drug: Vorinostat; Drug: Niacinamide

V/N: Level 4

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg

Drug: Vorinostat; Drug: Niacinamide

V/N: Level 5

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 100 mg/kg rounded to 100mg

Drug: Vorinostat; Drug: Niacinamide

V/N/E: Level 1

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg Etoposide: 25 mg/m2

Drug: Vorinostat; Drug: Niacinamide; Drug: Etoposide

V/N/E: Level 2

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg Etoposide: 50 mg/m2

Drug: Vorinostat; Drug: Niacinamide; Drug: Etoposide

V/N/E: Level 3

EXPERIMENTAL

Vorinostat: 400mg Niacinamide: 80 mg/kg rounded to 100mg Etoposide: 100 mg/m2

Drug: Vorinostat; Drug: Niacinamide; Drug: Etoposide

Interventions

Vorinostat DRUG

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.

Also known as: SAHA

V/N/E: Level 1; V/N/E: Level 2; V/N/E: Level 3; V/N: Level 1; V/N: Level 2; V/N: Level 3; V/N: Level 4; V/N: Level 5

Niacinamide DRUG

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.

Also known as: Nicotinamide

V/N/E: Level 1; V/N/E: Level 2; V/N/E: Level 3; V/N: Level 1; V/N: Level 2; V/N: Level 3; V/N: Level 4; V/N: Level 5

Etoposide DRUG

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."

Also known as: VP-16

V/N/E: Level 1; V/N/E: Level 2; V/N/E: Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Must have received first line chemotherapy. No upper limit to number of prior therapies
• Evaluable Disease
• Age \>18 years
• Eastern Cooperative Oncology Group (ECOG) performance status \<2
• Life expectancy of greater than 3 months
• Patients must have adequate organ and marrow function
• Adequate Contraception
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• 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
• Patients may not be receiving any other investigational agents
• Patients with known central nervous system metastases, including lymphomatous meningitis
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat, niacinamide or etoposide
• Uncontrolled intercurrent illness
• Pregnant women
• Nursing women
• 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
• Patient is known to be Human Immunodeficiency Virus (HIV)-positive
• Active Hepatitis A, Hepatitis B, or Hepatitis C infection
• Patient has a history of surgery that would interfere with the administration or absorption of the oral study drugs

Sponsors & Collaborators

• Columbia University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Center for Lymphoid Malignancies at CUMC

New York, New York, 10019, United States

Location

Related Publications (1)

• 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.

  PMID: 23913470 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Vorinostat; Niacinamide; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Owen A. O'Connor, MD, Ph.D.
• Organization: Columbia University Medical Center

oo2130@cumc.columbia.edu

212-326-5720

Study Officials

• Owen A O'Connor, MD, Ph.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 5, 2008
• Study Start: June 1, 2008
• Primary Completion: February 1, 2014
• Study Completion: March 1, 2015
• Last Updated: November 20, 2020
• Results First Posted: March 10, 2015

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)