• Safety, tolerability and maximum tolerated dose of orally administered PXD101 for each cohort [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
  

• Determine the pharmacokinetics of oral PXD101 when dosed once or twice daily at various dose levels [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  
• Explore anti-tumor activity [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  
• Determine the safety, tolerability, and anti-tumor activity of orally administered PXD101 to patients with lymphoma [ Time Frame: throughout the trial ] [ Designated as safety issue: Yes ]
  

Drug: belinostat
oral belinostat dosed once or twice daily at continuous and discontinuous dosing schedules.

Inclusion Criteria:

• Age ≥ 18 years
• Solid tumor: Histologically confirmed solid tumors.
• Lymphoma: relapsed or refractory B-cell or T-cell lymphoma, NK-cell lymphoma or Hodgkins disease
• At least one evaluable lesion. Lesions must be evaluated by computed tomography (CT), magnetic resonance imaging (MRI), or bone scan. Patients with prostate cancer, bone disease and rising prostate-specific antigen [PSA] but no other evaluable disease are eligible and will be evaluated based on PSA. For lymphoma patients, lesions can also be measured by PET and/or evaluated in peripheral blood or bone marrow.
• Progressive disease: Progressive disease will be defined as new or progressive lesions on CT-scan, MRI, bone scan or by rising PSA
• ≥ 4 weeks since prior radiation therapy or chemotherapy
• Karnofsky performance ≥ 60%

• Solid Tumor: Acceptable liver, renal and bone marrow function to include:

  • absolute neutrophil count ≥ 1.5 x 10^9/L
  • hemoglobin ≥ 9.0 g/dl
  • platelets ≥ 100 x 10^9/L
  • bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN is acceptable if liver has tumor involvement)
  • serum creatinine ≤ 1.5 x ULN
  • PT-INR/PTT ≤ 1.5 x ULN, or for patients on anticoagulation therapy, status within therapeutic range

• Lymphoma: Acceptable liver, renal and bone marrow function including the following:

  • absolute neutrophil count ≥ 1.0 x 10^9/L
  • platelets ≥ 50 x 10^9/L
  • bilirubin ≤ 1.5 x upper limit of normal (ULN), or ≤3 times ULN if documented hepatic involvement with lymphoma, or ≤5 times ULN if history of Gilbert's disease
  • AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN is acceptable if liver has tumor involvement)
  • serum creatinine ≤ 1.5 x ULN
  • PT-INR/PTT ≤ 1.5 x ULN, or in the therapeutic range if on anticoagulation therapy
• Serum potassium within normal range
• Estimated life expectancy of greater than 3 months
• Signed informed consent prior to any study specific procedures

Exclusion Criteria:

• Prior treatment with PXD101

• Within 4 weeks of enrollment:

  • major surgery
  • metastatic disease requiring palliative treatment

  • Anticancer therapy, including:

    • chemotherapy
    • radiotherapy
    • endocrine therapy
    • immunotherapy
    • other investigational agents (6 weeks for mitomycin or nitrosourea)
    • Lymphoma patients: No anticancer therapy within 2 weeks except for Rituximab which patients should be off for greater than 3 months unless there is evidence of disease progression.
• Serious concomitant systemic disorders (eg, active infection) compromising patient safety.
• Symptomatic brain metastases

• Significant cardiovascular disease, including:

  • unstable angina pectoris
  • uncontrolled hypertension
  • congestive heart failure (New York Heart Association [NYHA] Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy
  • ischemic or severe valvular heart disease
  • myocardial infarction within 6 months prior to the trial entry

• A marked baseline prolongation of QT/QTc interval, such as:

  • repeated demonstration of a QTc interval > 500 msec
  • Long QT syndrome
  • required use of concomitant medication on dosing days that may cause torsade de pointes
• Altered mental status precluding understanding of the informed consent process and/or completion of the study
• Pregnant or breast-feeding women
• Refusal or inability to use effective means of contraception (for men and women of childbearing potential)
• History of, or test positive for, HIV.
• Lymphoma patients who have relapsed within 100 days of autologous or allogenic transplantation.