Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma
A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma
7 other identifiers
interventional
37
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2005
Longer than P75 for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2005
CompletedFirst Submitted
Initial submission to the registry
November 11, 2005
CompletedFirst Posted
Study publicly available on registry
November 15, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2016
CompletedResults Posted
Study results publicly available
March 6, 2018
CompletedMarch 6, 2018
February 1, 2018
10.7 years
November 11, 2005
December 20, 2017
February 5, 2018
Conditions
Outcome Measures
Primary Outcomes (2)
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
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 Outcomes (4)
Change in Histone Acetylation by Immunohistochemistry (IHC)
Baseline to up to day 14
Change in Histone Acetylation by Western Blot (WB)
Baseline to up to day 14
2-Year Overall Survival
Until Death from any cause, up to 2 years
2-Year Progression Free-Survival
Until death or progression, up to 2 years
Study Arms (1)
Treatment (vorinostat)
EXPERIMENTALPatients 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.
Interventions
Given PO
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Related Publications (1)
Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. doi: 10.1200/JCO.2010.32.1398. Epub 2011 Feb 7.
PMID: 21300924DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Two enrolled patients were ineligible due to diffuse B-cell lymphoma at start of treatment. Their treatment was changed (within 2 months of enrollment) before a response evaluation. These patients were removed and are not included in the analysis.
Results Point of Contact
- Title
- Paul Frankel, Ph.D.
- Organization
- City of Hope
Study Officials
- PRINCIPAL INVESTIGATOR
Leslie Popplewell
City of Hope Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 11, 2005
First Posted
November 15, 2005
Study Start
September 1, 2005
Primary Completion
May 1, 2016
Study Completion
May 1, 2016
Last Updated
March 6, 2018
Results First Posted
March 6, 2018
Record last verified: 2018-02