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

July 9, 2018 updated by: City of Hope Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Beverly Hills, California, United States, 90211
        • Tower Cancer Research Foundation
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • Pasadena, California, United States, 91105
        • City of Hope Medical Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vorinostat and Rituximab
Vorinostat by mouth two times (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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (Complete and Partial Response)
Time Frame: After every 3 cycles, up to 1 year after the start of treatment
Response was assessed according to the 2007 Cheson criteria using CT scans or PET: Complete Response (CR), Disappearance of all evidence of disease; Partial Response (PR), >=50% decrease in the Sum of the Product of Diameters (SPD) of up to 6 largest dominant masses and no increase in the size of other nodes; Overall Response (OR) = CR + PR.
After every 3 cycles, up to 1 year after the start of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: Until disease progress\relapse, up to 1 year after the start of treatment
Progression\Relapse is defined using the 2007 Cheson criteria, as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy; or at least a 50% increase for nadir in the SPD of any previously involved nodes; or at least a 50% increase in the longest diameter of any singe previously identified node more than 1 cm in its short axis. Estimated using the product-limit method of Kaplan and Meier.
Until disease progress\relapse, up to 1 year after the start of treatment
Number of Participants With Grade 3 and 4 Toxicities
Time Frame: 3 weeks after the stop of treatment
Grade 3 & 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 3.0.
3 weeks after the stop of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)
Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Robert Chen, MD, City of Hope Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2008

Primary Completion (Actual)

June 8, 2017

Study Completion (Actual)

June 8, 2017

Study Registration Dates

First Submitted

July 22, 2008

First Submitted That Met QC Criteria

July 22, 2008

First Posted (Estimate)

July 23, 2008

Study Record Updates

Last Update Posted (Actual)

August 7, 2018

Last Update Submitted That Met QC Criteria

July 9, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07195
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CDR0000600989 (Registry Identifier: PDQ)
  • NCI-2010-00531 (Registry Identifier: NCI CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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