Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma

• Response rate based on the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
• Toxicity rates graded according to the Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

• Duration of response [ Time Frame: From the documented beginning of response (CR, CRu or PR) to the time of relapse, assessed up to 3 years ] [ Designated as safety issue: No ]
  Estimated using the Kaplan-Meier method.
• Progression-free survival [ Time Frame: From randomization to the first of progression, relapse, or death from any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  Estimated using the Kaplan-Meier method.

This phase II trial is studying how well sorafenib works in treating patients with recurrent diffuse large B-cell non-Hodgkin's lymphoma. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To evaluate the response rate of treatment with sorafenib (BAY43-9006) in patients with recurrent aggressive non-Hodgkin's lymphomas.

SECONDARY OBJECTIVES:

I. To evaluate the duration of response and progression free survival of treatment with BAY43-9006 in patients with recurrent aggressive Non-Hodgkin's Lymphomas.

II. To characterize the toxicity of treatment with BAY43-9006 in patients with recurrent aggressive Non-Hodgkin's Lymphomas.

III. To further characterize the pharmacokinetics properties of BAY43-9006 and assess influence of monooxygenases polymorphisms and MDR on pharmacokinetics.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Hepatosplenic T-cell Lymphoma
• Peripheral T-cell Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult T-cell Leukemia/Lymphoma
• Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Inclusion Criteria:

• Patients must have histologically confirmed recurrent de novo or transformed diffuse large B cell lymphoma (DLBCL) or one of its variants according to WHO classification (centroblastic, immunoblastic, T-cell/histiocyte rich and anaplastic variants)
• Patients must have no CNS involvement
• ECOG performance status must be 0 or 1
• Patients must have measurable disease as defined in section 6 assessed within 4 weeks of registration
• Patients must not have been previously treated with Sorafenib (BAY 43-9006) or other small molecule targeted inhibitors of MAPK signaling intermediates or angiogenesis (e.g. bevacizumab,/Avastin, oral MEK inhibitor CI-1040)
• Patients must have failed one or more prior NHL chemotherapy or antibody therapy with curative intent; autologous stem cell transplant is permitted
• Patients must not have progressed within 60 days of last therapy
• Patients must not have received prior allogeneic stem cell transplant
• Patients must not be candidates for potentially curative therapy, such as HSCT, OR must have refused these alternative therapies
• Patients must not be receiving any other investigational agents
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• Patients must not have uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
• Leukocytes >= 2,000/mm^3
• Absolute neutrophil count >= 1,000/mm^3
• Platelets >= 75,000/ mm^3
• Total bilirubin =< 2.0 X normal institutional limits
• AST =< 2.5 X institutional upper limit of normal
• ALT =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits; creatinine clearance calculated or measured at >= 60 ml/min/1.73m^2 if creatinine level is above institutional limits
• PT/INR Within Institutional limits of normal
• Patients with underlying hypertension as defined by blood pressures averaging greater than 140/90 on two separate clinic visits are eligible if hypertension has been controlled by standard nonpharmacologic and pharmacologic therapy
• Patients must not have active HIV infection, because of possible pharmacokinetic interactions of anti-retroviral therapy with BAY43-9006
• Patients must be physically able to orally ingest tablets
• Patients must not have any evidence of bleeding diathesis
• Patients must not be taking the cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine and phenobarbital), rifampin or St. John's Wort
• Women must not be pregnant or breast-feeding because the side effects of BAY43-9006 on developing embryos and nursing infants are unknown; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy

Exclusion Criteria:

• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception