| Study Summary: |
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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.
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| Criteria: |
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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
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