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

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00253630
• Other study ID #: NCI-2012-02843
• Secondary ID: NCI-2012-02843PH
• Status: Completed
• Phase: Phase 2
• First received: November 11, 2005
• Last updated: February 5, 2018
• Start date: September 2005
• Est. completion date: May 2016

Study information

• Verified date: February 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• 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

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Vorinostat
Given PO

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	City of Hope South Pasadena	South Pasadena	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate	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.	Up to 3 years
Primary	Number of Participants With Adverse Events	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.	Up to 3 years
Secondary	Change in Histone Acetylation by Immunohistochemistry (IHC)	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.	Baseline to up to day 14
Secondary	Change in Histone Acetylation by Western Blot (WB)	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.	Baseline to up to day 14
Secondary	2-Year Overall Survival	Estimated using the product-limit method of Kaplan and Meier.	Until Death from any cause, up to 2 years
Secondary	2-Year Progression Free-Survival	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.	Until death or progression, up to 2 years