Sorafenib in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

You may be eligible if

• Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) by NCI-WG immunophenotype and blood criteria
• * Documentation of current or prior peripheral blood (PB) or bone marrow (BM) immunophenotype compatible with CLL
• Intermediate-risk (Rai stage I or II) or high-risk (Rai stage III or IV) disease, including any of the following:
• * Rai stage I disease with lymphocytosis and enlarged nodes
• * Rai stage II disease with lymphocytosis plus splenomegaly and/or hepatomegaly (nodes positive or negative)
• * Rai stage III disease with lymphocytosis plus anemia
• * Rai stage IV disease with lymphocytosis and thrombocytopenia
• Must require treatment with active disease, experiencing disease related symptoms, or having deterioration of blood counts, meeting ≥ 1 of the following criteria:
• * Presence of ≥ 1 of the following disease-related symptoms:
• * Weight loss \> 10% within the past 6 months
• * Extreme fatigue (i.e., ECOG performance status 2: cannot work or unable to perform usual activities)
• * Fever \> 100.5°F for 2 weeks without evidence of infection
• * Night sweats without evidence of infection
• * Evidence of progressive marrow failure, as manifested by worsening of anemia (hemoglobin \< 10 g/dL), thrombocytopenia (platelet count \< 100,000/mm³), and/or neutropenia (neutrophil count \< 2,000/mm³)
• * Massive (i.e., \> 6 cm below left costal margin) or progressive splenomegaly or discomfort from splenomegaly
• * Massive nodes or clusters (i.e., \> 10 cm in longest diameter), progressive adenopathy, or discomfort from lymphadenopathy
• * Deterioration of blood counts and/or progressive lymphocytosis, with an increase of ≥ 10% documented over a 2-month period OR an anticipated doubling time \< 6 months
• Relapsed disease
• * Must receive at least 1, but no more than 3, prior chemotherapy regimens with any cytotoxic agent or antibody therapy
• * No fludarabine refractory disease
• * Responded to prior fludarabine without relapse or disease progression for at least 6 months
• Patients with a history of Coombs-positive hemolytic anemia are eligible provided recovery from treatment of hemolysis and off steroids
• No stage 0 CLL
• No known CNS involvement
• Life expectancy \> 6 months
• ECOG performance status 0-2 OR Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,000/mm³
• Platelets ≥ 30,000/mm³
• Bilirubin ≤ 2 mg/dL
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min (for patients with creatinine levels above normal)
• No currently active second malignancy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patient must use effective contraception prior to and during study participation
• No uncontrolled hypertension, defined as blood pressure (BP) \> 150/100 mm Hg on 2 different measurements at least 1 day apart with either systolic or diastolic number meeting this definition
• * Patients may later enter the study, if they have achieved stable BP (i.e., \< 140/90 mm Hg) on a regimen of ≤ 2 drugs after 6-8 weeks of therapy
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
• * Symptomatic congestive heart failure
• * Unstable angina pectoris
• * Cardiac arrhythmia
• * Psychiatric illness or social situations that would limit compliance with the study requirements
• No active infection requiring systemic antibiotics
• No evidence of bleeding diathesis
• No evidence of bowel perforation or obstruction risk
• No swallowing dysfunction leading to difficulty taking the study drug
• See Disease Characteristics
• Recovered from prior therapy
• At least 2 weeks since prior antibiotic therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
• At least 12 weeks since prior monoclonal antibody
• Concurrent warfarin for anticoagulation allowed provided all of the following are met:
• * On a stable therapeutic dose
• * INR ≤ 3
• * No active bleeding or pathological condition that carries high-risk of bleeding
• No prior MAPK signaling inhibitor agents or anti-angiogenesis agents
• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
• No other concurrent investigational agents