PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumor or lymphoma that is refractory to standard therapy or for which no standard therapy exists

• No active, untreated, or symptomatic brain metastases

  • Patients with treated brain metastases are eligible provided metastasis are stable and the patient is off all steroids and anticonvulsants
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of liver metastases)
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101, bortezomib, boron, or mannitol
• No peripheral neuropathy > grade 1

• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Psychiatric illness or social situation that would preclude study requirements

• No significant cardiovascular disease, including any of the following:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class III-IV heart failure
  • Unstable angina pectoris
  • Uncontrolled hypertension
  • Condition requiring antiarrhythmic therapy
  • Ischemic or severe valvular heart disease
  • Acute ischemia or active conduction system abnormalities by ECG
• No marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval > 500 msec), long QT syndrome, or required use of concurrent medication during PXD101 administration that may cause torsade de pointes
• No severe medical or psychiatric problems of that would preclude study compliance
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin C)
• At least 4 weeks since prior radiotherapy and recovered
• At least 2 weeks since prior palliative radiotherapy to sites involving < 35% of bone marrow reserve
• At least 4 weeks since prior investigational agents
• At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
• No prior stem cell or bone marrow transplantation
• No concurrent radiotherapy or immunotherapy

• No concurrent hormonal therapy

  • Luteinizing hormone-releasing hormone agonists, selective estrogen receptor modulators, or aromatase inhibitors as chronic maintenance therapy allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies