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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00253630
First received: November 11, 2005
Last updated: July 28, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Drug: vorinostat
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (complete remission + partial remission) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Exact binomial 95% confidence intervals will be provided.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Recorded by type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

  • Change in histone acetylation by immunohistochemistry (IHC) and Western Blot (WB) [ Time Frame: Baseline to up to day 14 ] [ Designated as safety issue: No ]
    Histone acetylation by IHC will be scored as -, +, ++, or +++, reflecting both the intensity of staining as well as the number of cells stained; and histone acetylation by WB will recorded as the ratio of acetylated histone (measured by photodensitometry) divided by the total histone (H3 or H4), in order control for the amount of protein loaded. Analysis will be primarily descriptive, with the goal of describing baseline distributions and estimating the frequency and degree of changes from baseline.


Estimated Enrollment: 33
Study Start Date: September 2005
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00253630

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
City of Hope Medical Group Inc
Pasadena, California, United States, 91105
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Leslie Popplewell Beckman Research Institute
  More Information

No publications provided by National Cancer Institute (NCI)

Additional 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, PHII-63, 6963, N01CM17101, U01CA062505, P30CA033572, N01CM62209
Study First Received: November 11, 2005
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 28, 2014