RATIONALE: Suberoylanilide hydroxamic acid may stop the growth of cancer cells by blocking
some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well suberoylanilide hydroxamic acid works in
treating patients with relapsed B-cell non-Hodgkin's lymphoma.
- Determine the antitumor effectiveness of suberoylanilide hydroxamic acid, as measured by
overall objective response rate, in patients with relapsed diffuse large B-cell
lymphoma.
- Determine the duration of response and time to response in patients treated with this
- Determine progression-free survival, time to progression, and 3- and 6-month
- Determine the safety of this drug in these patients.
Patients receive oral suberoylanilide hydroxamic acid twice daily on days 1-14. Treatment
repeats every 21 days for up to 8 courses in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed within 4 weeks and then every 6-12
months thereafter.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within approximately
1 year.
DISEASE CHARACTERISTICS:
- Histologically confirmed diffuse large B-cell lymphoma
- De novo or transformed* disease NOTE: *Patients with transformed diffuse large
B-cell lymphoma must meet WHO criteria for diffuse large cell lymphoma on last
biopsy prior to study entry AND have ≥ 1 prior histological diagnosis of
follicular disease
- Relapsed disease, defined as recurrent or progressive disease after standard
first-line chemotherapy (e. g., CHOP or an anthracycline-containing regimen equivalent)
AND 1 systemic salvage therapy that may have included autologous stem cell
transplantation
- Patients who are not candidates for systemic salvage and/or stem cell
transplantation are eligible
- Must have had a response that lasted ≥ 3 months OR stable disease that lasted ≥ 3
months after completion of the most recent treatment
- Failed no more than 3 prior treatment regimens
- Pre-induction chemotherapy and autologous stem cell transplantation are
considered 1 therapy
- Antibody therapy (e. g., rituximab) given in combination with or as consolidation
therapy after a chemotherapy regimen (without intervening relapse) is considered
1 therapy
- Antibody therapy given as a single agent is considered 1 therapy
- Measurable disease, defined as 1 unidimensionally measurable lesion ≥ 2 cm by
conventional CT scan OR ≥ 1 cm by spiral CT scan
- No active brain or leptomeningeal metastases, as indicated by positive cytology from
lumbar puncture or CT scan or MRI
- Previously treated CNS disease allowed provided there is negative cytology from
lumbar puncture
- No known HIV-related malignancy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 75,000/mm^3
Hepatic
- Bilirubin < 1. 5 times upper limit of normal (ULN)
- AST and ALT ≤ 2. 5 times ULN (5 times ULN if liver is involved by tumor)
- No active hepatitis B or C infection
Renal
- Not specified
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Immunologic
- No acute infection requiring IV antibiotics or antiviral or antifungal agents within
the past 2 weeks
- No ongoing or active infection
- No known HIV positivity
- No known allergy to any component of the study drug
- No acute or chronic graft-vs-host disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception during and for 14
days after completion of study treatment
- No other malignancy within the past 5 years except basal cell carcinoma or carcinoma
in situ of the cervix
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No circumstance that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- At least 4 weeks since prior biologic therapy
- No prior allogeneic stem cell transplantation
- No concurrent prophylactic growth factors
- No concurrent anticancer biologic therapy
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy
- No concurrent anticancer chemotherapy
Endocrine therapy
- Concurrent systemic steroids allowed provided the dosage has been stabilized to the
equivalent of ≤ 10 mg/day of prednisone for ≥ 4 weeks prior to study entry
Radiotherapy
- At least 4 weeks since prior radiotherapy
- No concurrent anticancer radiotherapy
Surgery
- At least 4 weeks since prior major surgery
- No prior gastrointestinal resection or procedure that may affect drug absorption
Other
- Recovered from prior therapy
- At least 4 weeks since prior investigational therapy
- No prior histone deacetylase inhibitors (e. g., FR901228, MS-275, or LAQ-824)
- No concurrent vitamins except a single daily multivitamin
- No other concurrent investigational anticancer therapy
