PXD101 in Treating Patients With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

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.

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 < 2 times upper limit of normal (ULN) OR creatinine clearance >= 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