Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Sorafenib
Intervention description: Sorafenib 400mg orally twice daily will be administered for three cycles (1 cycle = 28 days). Subjects without significant toxicity or progressive disease may elect to continue treatment for a total of twelve cycles.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase 2 trial to evaluate the activity of sorafenib in relapsed or refractory CLL
      patients with an iwCLL-WG indication to receive therapy.

      Sorafenib is an orally active multikinase inhibitor, which targets the RAF/MEK/ERK signaling
      pathway as well as several receptor tyrosine kinases. It is FDA approved for the treatment of
      hepatocellular carcinoma and renal cell carcinoma. Preclinical studies in the investigators
      laboratory demonstrated that sorafenib is cytotoxic to CLL cells.

      The primary objective of the study is to determine the overall response rate of Sorafenib in
      previously treated CLL patients. All patients will receive sorafenib at 400 mg twice daily
      continuously for three months and then assessed for response. Responding patients may elect
      to continue on treatment for an additional 9 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of relapsed or refractory CLL.

          -  Experiencing progressive disease with an iwCLL-WG indication to receive therapy.

          -  Age ≥ 18 years.

          -  ECOG performance status ≤ 2 at study entry.

          -  Adequate organ and marrow function as defined below:

          -  platelets ≥ 50 x 109/L

          -  serum creatinine ≤ 1.5 mg/dL

          -  total bilirubin ≤ 1.5 mg/dL

          -  AST(SGOT)/ALT(SPGT) ≤ 2 X institutional upper limit of normal or if known liver
             involvement <5X institutional upper limit of normal

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation, and for 90 days following completion of therapy.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately.

          -  Ability to understand and the willingness to sign a written informed consent.

        Exclusion Criteria:

          -  No investigational agents within 28 days prior to entering the study.

          -  No concurrent use of other anti-cancer agents or treatments.

          -  No congestive heart failure > class II NYHA. Patients must not have unstable angina
             (anginal symptoms at rest) or new onset angina (beginning within the last 3 months) or
             myocardial infarction within the past 6 months.

          -  No known brain metastases (progressive neurologic dysfunction may confound the
             evaluation of neurologic and other adverse events).

          -  No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

          -  No uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or
             diastolic pressure > 90 mmHg, despite optimal medical management.

          -  No known active Hepatitis or HIV.

          -  No history of allergic reactions attributed to compounds sorafenib or its excipients.

          -  No uncontrolled intercurrent illness such as ongoing or active infection (fungal,
             bacterial, and/or viral), CTCAE grade 2 or greater.

          -  No thrombolic or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months.

          -  No serious non-healing wound, ulcer, or bone fracture.

          -  No major surgery, open biopsy or significant traumatic injury within 4 weeks of first
             study drug.

          -  No condition that may impair the patient's ability to swallow whole pills.

          -  Patient must not have any malabsorption problem.

          -  Patients receiving St. John's Wort or rifampin (rifampicin) are ineligible.

          -  Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
             thrombocytopenia (ITP) are ineligible.

          -  Patients must not be experiencing psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Patients must not be pregnant or nursing due to the potential for congenital
             abnormalities and the potential of this regimen to harm nursing infants.

          -  Subjects with any previously untreated or concurrent cancer that is distinct in
             primary site or histology from CLL except cervical cancer in-situ, treated basal cell
             carcinoma, squamous cell carcinoma of the skin, or superficial bladder tumor (Ta and
             Tis). Subjects surviving a cancer that was curatively treated and without evidence of
             disease for more than 3 years before study entry are allowed. All cancer treatments
             must be completed at least 3 years prior to study entry (ie, signature date of the
             informed consent form).