Intervention: Sorafenib
Trial phase: Phase 2
ATC code: L01EX02 | L01XE05
SMILES: CNC(=O)c1cc(Oc2ccc(NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)cc2)ccn1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 5
Group description: Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Eligibility criteria:
Inclusion Criteria:

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

Patients who currently do not have > 5,000/mm³ absolute lymphocytosis are eligible if they have previously met PB lymphocytosis criteria and have a current immunophenotype documenting monoclonal B lymphocytosis morphologically and immunophenotypically 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