pxd101 in treating patients with relapsed or refractory aggressive b-cell non-hodgkin's lymphoma

Conditions: Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma

Summary: this phase ii trial is studying how well pxd101 works in treating patients with relapsed or refractory aggressive b-cell non-hodgkin's lymphoma. pxd101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

primary objectives: i. evaluate response rate in patients with relapsed or refractory aggressive b-cell non-hodgkin's lymphoma treated with pxd101. secondary objectives: i. determine the toxicity of this drug in these patients. ii. estimate the 6-month progression-free survival rate in patients treated with this drug. tertiary objectives: i. determine the major histocompatability complex of class ii proteins (hla-dr, -dp, -dq), tunel, and cd8 infiltration status, by immunochemistry on paired pre- and post-treatment tumor samples, in the first 20 patients enrolled. ii. measure ciita and hla-dr mrna expression using quantitative reverse transcriptase-polymerase chain reaction and determine, preliminarily, the associations of these markers with progression-free survival. iii. evaluate paired pre- and post-treatment peripheral blood mononuclear cells from patients for histone acetylation status and determine correlation with findings from duplicate experiments on pre- and post-needle core biopsies. outline: this is a multicenter study. patients receive pxd101 iv over 30 minutes on days 1-5. treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. needle core biopsies and peripheral blood mononuclear cells are obtained from the first 20 patients pre- and post-treatment for biomarker correlative studies. after completion of study treatment, patients are followed every 3-6 months for up to 3 years.

Eligibility criteria:
inclusion criteria: * biopsy-proven (no needle aspirations or cytologies) aggressive b-cell non-hodgkin's lymphoma (nhl), including 1 of the following histology subtypes: * diffuse large cell nhl * burkitt's or burkitt-like nhl * primary mediastinal nhl * relapsed or refractory disease * bidimensionally measurable disease * transformed nhl allowed * not eligible for stem cell transplantation (for patients registered to study at first relapse) * no active cns involvement by lymphoma * zubrod performance status 0-2 * no history of allergic reactions attributed to compounds of similar chemical or biologic composition to pxd101 * absolute neutrophil count \>= 1,500/mm\^3 * platelet count\>=100,000/mm\^3 * wbc \>= 3,000/mm\^3 * creatinine \ = 60 ml/min * no significant ekg abnormalities * bilirubin normal * sgot/sgpt \< 2.5 times uln (=\< 5 times uln if liver involvement) * no long qt syndrome or marked baseline prolongation of qt/qtc interval (e.g., repeated demonstration of qtc interval \> 500 msec) * no other significant cardiovascular disease, including any of the following: * unstable angina pectoris * uncontrolled hypertension * congestive heart failure related to primary cardiac disease * any condition requiring anti-arrhythmic therapy * ischemic or severe valvular heart disease * myocardial infarction within the past 6 months * no major surgery within 28 days prior to study entry * no concurrent combination antiretroviral therapy for hiv-positive patients * no concurrent medication that may cause torsades de pointes (i.e., prolongation of the qt interval \> 500 msec) * at least 14 days since prior radiotherapy * at least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor * no clinical evidence of any of the following: * severe peripheral vascular disease * diabetic ulcers or venous stasis ulcers * history of deep venous or arterial thrombosis within the past 3 months * radioimmunotherapy is considered a chemotherapy regimen * single-agent rituximab is not considered a chemotherapy regimen * standard salvage chemotherapy followed by autologous stem cell transplantation is considered 1 regimen * no known aids or hiv-associated complex * not pregnant or nursing * fertile patients must use effective contraception * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix * at least 2 weeks since prior therapy and recovered * no more than 5 prior chemotherapy regimens