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

PRIMARY OBJECTIVES:

I. Determine the overall response rate, including complete and partial responses, in patients with chemosensitive, relapsed, aggressive, non-Hodgkin's lymphoma treated with sorafenib.

SECONDARY OBJECTIVES:

I. Determine progression-free and overall survival of patients treated with this drug.

II. Determine response duration in patients treated with this drug.

OUTLINE: This is an open-label study.

Patients receive oral sorafenib twice daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Inclusion criteria

• Histologically or cytologically confirmed aggressive* non-Hodgkin's lymphoma by excisional-node biopsy or core needle biopsy and bone marrow biopsy, including 1 of the following types:

• Mantle cell lymphoma
• Primary mediastinal large B-cell lymphoma
• Diffuse large B-cell lymphoma
• Anaplastic large cell lymphoma (T-cell or null-cell type)
• Recurrent disease
• Patients must have received ≥ 1 induction regimen containing anthracyclines (e.g., CHOP [with or without rituximab] or R-EPOCH)
• Chemosensitive disease at the time of relapse

• Patients who responded with a complete or partial remission that lasted at least 8 weeks after their last chemotherapy regimen are considered chemosensitive
• Measurable disease, defined as a lymph node or a nodal mass of > 1 cm in its longest transverse diameter on CT scan
• Ineligible for, refused, or relapsed after stem cell transplant (for patients with non-mantle cell lymphoma)
• No known brain metastases, including meningeal involvement
• ECOG performance status (PS) 0-2
• Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Fertile patients must use effective contraception
• Not pregnant or nursing
• Negative pregnancy test
• No uncontrolled illness
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• No known positive HIV serology
• No inflammatory bowel disease
• No swallowing dysfunction that would prevent ingestion of pills
• No hemorrhagic diathesis
• No ongoing or active infection
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No uncontrolled hypertension
• No psychiatric or social situation that would limit compliance with study requirements
• No poorly controlled medical condition that would seriously complicate compliance with this study
• Patients with inflammatory or exfoliative skin disease are excluded (regardless of the extent of the involvement) unless the skin condition is lymphoma related
• See Disease Characteristics
• Previous treatment-related toxic effects should be resolved to grade 1 or better
• No chemotherapy or radiation therapy within the past 4 weeks

• 6 weeks for nitrosoureas or mitomycin C
• No prior antibody therapy for at least 3 months
• Prior radiation for localized disease or total body irradiation as part of a conditioning regimen prior to stem cell transplant allowed
• Prior radio-immunotherapy allowed
• No concurrent therapeutic anticoagulation

• Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices are acceptable provided that the requirements for PT, INR, and PTT are met
• No concurrent use of another investigational agent
• No concurrent use of the following drugs: phenytoin, carbamazepine, phenobarbital, rifampin, or Hypericum perforatum (St. John's wort)
• No other concurrent anticancer therapy