ClinicalTrials.gov
ClinicalTrials.gov Menu

Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00253630
Recruitment Status : Completed
First Posted : November 15, 2005
Results First Posted : March 6, 2018
Last Update Posted : March 6, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well vorinostat works in treating patients with relapsed or refractory indolent non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Nodal Marginal Zone Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Other: Laboratory Biomarker Analysis Drug: Vorinostat Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the anti-tumor activity of SAHA (vorinostat) as assessed by the objective response rate, time to progression and survival in subjects with advanced lymphoma.

II. To assess the toxicity profile of SAHA in this patient population. III. To perform correlative laboratory investigations to confirm modulation of chromatin acetylation as the biologic target and attempt to gain insight into the downstream molecular mechanisms involved in the induction of apoptosis mediated by SAHA.

OUTLINE:

Patients receive vorinostat orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma
Study Start Date : September 2005
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016


Arm Intervention/treatment
Experimental: Treatment (vorinostat)
Patients receive vorinostat PO BID on days 1-14. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Vorinostat
Given PO
Other Names:
  • L-001079038
  • MSK-390
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza



Primary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 3 years ]
    Radiological assessment by CT and/or PET scan after every three cycles (every 3 months). Response assessed by the standard Cheson criteria (Cheson et al, J Clin Oncol 17:1244, 1999). Complete Remission (CR) - (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative (b) Variably FDG-avid or PET negative; regression to normal size on CT; Partial Remission (PR) - 50% or greater decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Response Rate = CR + PR.

  2. Number of Participants With Adverse Events [ Time Frame: Up to 3 years ]
    Grades 3 & 4 adverse events definitely, probably or possibly related to treatment, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.


Secondary Outcome Measures :
  1. Change in Histone Acetylation by Immunohistochemistry (IHC) [ Time Frame: Baseline to up to day 14 ]
    Histone acetylation by IHC will be scored as -, +, ++, or +++, reflecting both the intensity of staining as well as the number of cells stained. Analysis will be descriptive, with the goal of describing baseline distributions and estimating the frequency and degree of changes from baseline.

  2. Change in Histone Acetylation by Western Blot (WB) [ Time Frame: Baseline to up to day 14 ]
    Histone acetylation by WB will be recorded as the ratio of acetylated histone (measured by photodensitometry) divided by the total histone (H3 or H4), in order to control for the amount of protein loaded. Analysis will be descriptive, with the goal of describing baseline distributions and estimating the frequency and degree of changes from baseline.

  3. 2-Year Overall Survival [ Time Frame: Until Death from any cause, up to 2 years ]
    Estimated using the product-limit method of Kaplan and Meier.

  4. 2-Year Progression Free-Survival [ Time Frame: Until death or progression, up to 2 years ]
    Estimated using the product-limit method of Kaplan and Meier. Progression defined as any new lesion or increase by greater than 50% of previously involved sites from nadir.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed relapsed/refractory indolent Non-Hodgkin's lymphoma (Included in this category are relapsed/refractory follicular center lymphomas grade I, II, III, relapsed /refractory marginal zone B-cell lymphoma (nodal and extranodal), relapsed/refractory mantle cell lymphoma)
  • Patients must have measurable disease by computed tomography (CT) scan. positron emission tomography (PET) scan evaluations are desirable but not mandatory, so that patients with negative PET scans but measurable disease by CT are eligible
  • Patients may have had up to four prior chemotherapeutic regimens; steroids alone and local radiation do not count as regimens (radiotherapy must have been completed at least 14 days prior to starting SAHA); rituxan alone does not count as a regimen, however, Bexxar or Zevalin do; the most recent therapy must have failed to induce a complete response, or there must be disease progression or recurrence after the most recent therapy
  • Patients may be enrolled who relapse after autologous stem cell transplant if they are at least three months after transplant, and after allogeneic transplant if they are at least six months post transplant; to be eligible after either type of transplant, patients must have achieved platelet counts greater than 100,000/mcL, and white blood cell (WBC) greater than 1,000/mcL at some point after their transplant, and should have no active related infections (i.e. fungal or viral); in the case of allogeneic transplant relapse, there should be no active acute graft versus host disease (GvHD) of any grade, and no chronic graft versus host disease other than mild skin, oral, or ocular GvHD not requiring systemic immunosuppression
  • Life expectancy of greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status #2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's Disease, are eligible
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine up to and including 2 mg/dl
  • Premenopausal women must have a negative serum pregnancy test prior to entry on this study; the effects of SAHA on the developing human fetus at the recommended therapeutic dose are unknown; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy within 4 weeks, rituximab within three months (unless there is evidence of progression) or radiotherapy within 2 weeks or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded; this does not include use of steroids, which may continue until two days prior to enrollment; low dose chlorambucil should be stopped two weeks prior to beginning SAHA; valproic acid should be stopped at least two weeks prior to enrollment; nitrosoureas and mitomycin should be stopped 6 weeks prior to enrollment
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases are excluded from this clinical trial unless the metastases are controlled after therapy and have not been treated with steroids within the past two months
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA
  • There must be no plans for the patient to receive concurrent hormonal, biological or radiation therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with SAHA
  • Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible
  • Patients with other active malignancies are ineligible for this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00253630


Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
City of Hope South Pasadena
South Pasadena, California, United States, 91030
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Leslie Popplewell City of Hope Comprehensive Cancer Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00253630     History of Changes
Other Study ID Numbers: NCI-2012-02843
NCI-2012-02843 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PHII-63
PHII-63 ( Other Identifier: City of Hope Comprehensive Cancer Center )
6963 ( Other Identifier: CTEP )
N01CM17101 ( U.S. NIH Grant/Contract )
P30CA033572 ( U.S. NIH Grant/Contract )
U01CA062505 ( U.S. NIH Grant/Contract )
N01CM62209 ( U.S. NIH Grant/Contract )
First Posted: November 15, 2005    Key Record Dates
Results First Posted: March 6, 2018
Last Update Posted: March 6, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Vorinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action