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

Primary Purpose

Hodgkin's Disease, Non-Hodgkin's Lymphoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Vorinostat

Niacinamide

Etoposide

About this trial

This is an interventional treatment trial for Hodgkin's Disease focused on measuring Hodgkin's Disease, Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Center for Lymphoid Malignancies at CUMC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

V/N: Level 1

V/N: Level 2

V/N: Level 3

V/N: Level 4

V/N: Level 5

V/N/E: Level 1

V/N/E: Level 2

V/N/E: Level 3

Arm Description

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

The Greatest Number of Cycles Received in Each Treatment Group

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

The Prevalence of Anti-tumor Activity

Pharmacodynamic Markers of Target Effect in Paired Tissue Biopsies

Full Information

NCT ID

NCT00691210

First Posted

June 3, 2008

Last Updated

November 5, 2020

Sponsor

Columbia University

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00691210

Brief Title

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

Acronym

SAHA

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 Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Columbia University

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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 maximum tolerated dose (MTD) is determined.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hodgkin's Disease, Non-Hodgkin's Lymphoma

Keywords

Hodgkin's Disease, Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

V/N: Level 1

Arm Type

Experimental

Arm Description

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

Arm Title

V/N: Level 2

Arm Type

Experimental

Arm Description

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

Arm Title

V/N: Level 3

Arm Type

Experimental

Arm Description

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

Arm Title

V/N: Level 4

Arm Type

Experimental

Arm Description

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

Arm Title

V/N: Level 5

Arm Type

Experimental

Arm Description

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

Arm Title

V/N/E: Level 1

Arm Type

Experimental

Arm Description

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

Arm Title

V/N/E: Level 2

Arm Type

Experimental

Arm Description

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

Arm Title

V/N/E: Level 3

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Vorinostat

Other Intervention Name(s)

SAHA

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.

Intervention Type

Drug

Intervention Name(s)

Niacinamide

Other Intervention Name(s)

Nicotinamide

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

VP-16

Intervention Description

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."

Primary Outcome Measure Information:

Title

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

Time Frame

3 years

Secondary Outcome Measure Information:

Title

The Greatest Number of Cycles Received in Each Treatment Group

Description

The highest number of cycles received by an individual participant in the treatment groups. Each cycle was 21 days long.

Time Frame

up to 45 weeks

Title

The Number of Dose Delays and Reductions at the MTD

Time Frame

continuous

Title

The Prevalence of Anti-tumor Activity

Time Frame

continuous

Title

Pharmacodynamic Markers of Target Effect in Paired Tissue Biopsies

Time Frame

continuous

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Owen A O'Connor, MD, Ph.D.

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Center for Lymphoid Malignancies at CUMC

City

New York

State/Province

New York

ZIP/Postal Code

10019

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23913470

Citation

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.

Results Reference

derived

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

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