Phase II Study of PXD101 (NSC-726630) in Relapsed and Refractory Aggressive B-Cell Lymphomas
Phase II Study of PXD101 (NSC-726630) in Relapsed and Refractory Aggressive B-Cell Lymphomas
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.
Inclusion Criteria:
Biopsy-proven (no needle aspirations or cytologies) aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the following histology subtypes:
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:
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:
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
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