Vorinostat and Rituximab in Treating Patients With Indolent Non-Hodgkin Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: rituximab; vorinostat
Intervention description: Rituximab will be administered at a dose of 375 mg/m2 on day 1 of every cycle, every 3 weeks.; 200 mg twice daily, orally for 14 days followed by a seven day break on a 21 day cycle.
Intervention MeSH terms: Rituximab; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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; stage I mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma

Summary:

      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.
    

Eligibility 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