RATIONALE: 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.
PURPOSE: This phase II trial is studying how well vorinostat works in treating patients with
relapsed or refractory indolent non-Hodgkin's lymphoma.
- Determine the time to disease progression in patients with relapsed or refractory
- Determine the objective response rate in patients treated with this drug.
- Determine the toxic effects of this drug in these patients.
Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days
for up to a total of 12 courses in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed indolent non-Hodgkin's lymphoma, including
the following subtypes:
- Grade 1, 2, or 3 follicular lymphoma
- Marginal zone B-cell lymphoma
- Nodal or extranodal
- Mantle cell lymphoma
- Measurable disease by CT scan
- Relapsed or refractory disease
- Disease progression or recurrence after most recent therapy OR failure to induce
a complete response after most recent therapy
- No known brain metastases
- Previously treated brain metastases that are currently asymptomatic without
steroids allowed
PATIENT CHARACTERISTICS:
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin normal (patients with elevated unconjugated bilirubin [e. g., Gilbert's
disease] allowed)
- AST and ALT ≤ 2. 5 times upper limit of normal
Renal
- Creatinine ≤ 2 mg/dL
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
Immunologic
- No known HIV infection
- No active or ongoing infection
- No history of allergic reaction to compounds of similar chemical or biologic
composition to vorinostat
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- No other active malignancy
- No active graft-vs-host disease (GVHD)
- No chronic GVHD except mild skin, oral, or ocular GVHD with no requirement for
systemic immunosuppression
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- See Chemotherapy
- More than 3 months since prior rituximab (unless there is evidence of progression)
- At least 3 months since prior autologous stem cell transplantation
- At least 6 months since prior allogeneic stem cell transplantation
- No concurrent biologic therapy
- No concurrent sargramostim (GM-CSF) or filgrastim (G-CSF)
- Concurrent epoetin alfa or darbepoetin alfa therapy for lymphoma-related anemia
allowed provided it is initiated before the start of study therapy
Chemotherapy
- No more than 4 prior chemotherapeutic regimens
- Steroids alone, rituximab alone, or local radiation is not considered 1 regimen
- Iodine I 131 tositumomab OR ibritumomab tiuxetan alone is considered 1 regimen
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- At least 2 weeks since prior low-dose chlorambucil
- No other concurrent chemotherapy
Endocrine therapy
- See Disease Characteristics
- See Chemotherapy
- At least 2 days since prior steroid therapy
- At least 2 months since prior steroids for the treatment of brain metastases
- No concurrent hormonal therapy
Radiotherapy
- See Disease Characteristics
- See Chemotherapy
- More than 2 weeks since prior radiotherapy
- No concurrent radiotherapy
Other
- Recovered from prior therapy
- At least 2 weeks since prior valproic acid
- No concurrent antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
- No concurrent complementary or alternative medicines except routine vitamin
supplements
