Clinical trial NCT00303966 (phase 2, status: terminated)
Conditions: refractory chronic lymphocytic leukemia, stage i chronic lymphocytic leukemia, stage ii chronic lymphocytic leukemia, stage iii chronic lymphocytic leukemia, stage iv chronic lymphocytic leukemia
ICD codes: A87.2, K52.832, D72.111, C91.11, C91.12, C91.10, C91.11, C91.12, C91.10, C91.11, C91.12, C91.10, C91.11, C91.12, C91.10, C91.11, C91.12, C91.10
Drugs: sorafenib tosylate
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Reason stopped: 
    slow accrual
  
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