Vorinostat and Rituximab in Treating Patients With Indolent Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00720876
First received: July 22, 2008
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving vorinostat together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving vorinostat together with rituximab and to see how well it works in treating patients with indolent non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: vorinostat
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 Vorinostat (Suberoylanilide Hydroxamic Acid) Plus Rituximab in Indolent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Response rate (complete and partial response) [ Time Frame: 1 year after the start of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Time Frame: 1 year after the start of treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 1 year after the start of treatment ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 3 weeks after the stop of treatment ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Effects of treatment on systemic levels of immune cytokines, evaluated by cytokine bead array using Luminex X-MAP bead array technology [ Time Frame: Baseline and on day 14 ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: June 2008
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorniostat and Rituximab
Vorinostat by mouth 2X per day for two weeks followed by one week of rest. Rituximab intravenously once every three weeks .
Biological: rituximab
Rituximab will be administered at a dose of 375 mg/m2 on day 1 of every cycle, every 3 weeks.
Drug: vorinostat
200 mg twice daily, orally for 14 days followed by a seven day break on a 21 day cycle.

Detailed Description:

OBJECTIVES:

  • To evaluate the anti-tumor activity of vorinostat and rituximab, in terms of objective response rate, time to progression, and survival, in patients with indolent non-Hodgkin lymphoma.
  • To assess the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive oral vorinostat twice daily on days 1-14 and rituximab IV on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

  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 indolent Non-Hodgkin's Lymphoma; included in this category are newly diagnosed or 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 vorinostat); Rituxan alone does not count as a regimen; however, Bexxar or Zevalin do; for treated patients, the most recent therapy must have failed to induce a complete response (i.e., there is persistent disease by CT or PET), 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 month post transplant; to be eligible after either type of transplant, patients 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 glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal

Creatinine up to and including 2 mg/dl

Pre-menopausal women must have a negative serum pregnancy test prior to entry on this study; 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, 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 vorinostat; 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 vorinostat

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 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 mother is treated with vorinostat

Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible; in addition, HIV patients not receiving combination antiretroviral therapy are also ineligible

Patients with other active malignancies are ineligible for this study

Patients with preexisting or previous coagulation issues are not excluded from study as long as 1) previous pulmonary embolism or deep vein thrombosis have been adequately treated or 2) if they are actively receiving Coumadin or lovenox for anticoagulation; patients who are already on coumadin or lovenox do not need to take additional 40 mg subcutaneous injections daily

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720876

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
Sponsors and Collaborators
City of Hope Medical Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Robert Chen, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00720876     History of Changes
Other Study ID Numbers: 07195, P30CA033572, CDR0000600989, NCI-2010-00531
Study First Received: July 22, 2008
Last Updated: December 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
contiguous stage II marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma
stage I marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
recurrent mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Vorinostat
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014