Clinical Trial of PXD101 in Patients With T-Cell Lymphomas

Inclusion Criteria:

• Male or female with age > or = to 18 years.
• histologically confirmed diagnosis of cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL) or other T-cell non-Hodgkin's lymphoma (NHL).
• Must have failed at least one line of prior systemic therapy. No limitation in number of prior therapies. CTCL patients who are refractory or intolerant to oral Targretin are also eligible.
• The presence of measurable disease (defined as > or = to 1 cm with radiographic imaging) for PTCL or stage 1B or greater disease for CTCL and assessable by the severity-weighted assessment tool (SWAT).

• Adequate bone marrow and hepatic function including the following:

  • Absolute neutrophil count > or = to 1,000 cells/mm3, platelets > or = to 40,000/mm3
  • Total bilirubin < or = to 1.5 x upper normal limit or < or = 3 x upper normal limit if hepatic involvement
  • AST (SGOT) (aspartate aminotransferase), ALT (SGPT) (alanine aminotransferase) < or = to 2.5 x upper normal limit (< or = 5 x upper normal limit if hepatic involvement)
  • Hemoglobin > or = 9.0 g/dL.
• Serum potassium within normal range.
• Karnofsky performance status > or = to 70%.
• Estimated life expectancy > 3 months.
• Signed informed consent approved by the Institutional Review Board (IRB).

Exclusion Criteria:

• Patients who have received anti-cancer therapies within 4 weeks of first PXD101 administration should be excluded unless toxicity from prior anti-cancer therapy has resolved or returned to baseline and cancer disease status warrants.
• Any use of investigational drugs within 4 weeks prior to study registration.
• Major surgery within 4 weeks of study drug administration.
• Prior allogeneic bone marrow transplant.
• A diagnosis of adult T-cell lymphoma/leukemia (ATLL) or precursor T-lymphoblastic lymphoma.
• Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures. However, patients with progressing CTCL whose open skin lesions are frequently infected may not be excluded from this trial at the discretion of Investigators.
• Clinically significant cardiovascular disease left or ventricular ejection fraction < 40% (by echocardiogram [ECHO] or multigated acquisition scan [MUGA]) within 3 months of study enrollment.
• A marked baseline prolongation of QT/QTc ((corrected) QT) interval.
• Patients with renal insufficiency defined as a calculated creatinine clearance of < 45 mL/min/1.73 m2.
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biological composition to PXD101 and L-arginine.
• Clinically significant central nervous system disorders with altered mental status or psychiatric disorders precluding understanding of the informed consent process and/or completion of the necessary studies.
• Patients requiring treatment for other malignant diseases or less than 5 years post-treatment completion for an invasive malignant disease (excluding non-melanotic skin cancers or cervical cancer in-situ). Patients with any history of melanoma should be excluded.
• Pregnant or breast-feeding women, and women of childbearing age and potential, who are not willing to use effective contraception. Male patients and/or their fertile female partners who are not willing to use contraceptives during the trial.
• Known infection with HIV, human T-cell leukemia virus type-1 (HTLV-1), hepatitis B or hepatitis C.