Sunitinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Inclusion Criteria:

• Diagnosis of 1 of the following:

  • Biopsy proven small lymphocytic lymphoma (SLL)

  • Chronic lymphocytic leukemia (CLL) meeting all of the following criteria:

    • Peripheral blood lymphocyte count > 5,000/mm^3
    • Lymphocytes must consist of small to moderate size lymphocytes, with < 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically

    • Immunophenotyping consistent with CLL, defined by the following criteria:

      • Predominant population of lymphocytes share both B-cell antigens (i.e., CD19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (e.g., CD3 or CD2)
      • Dim surface immunoglobulin expression
      • Exclusively kappa and lambda light chains
      • Splenomegaly, hepatomegaly, or lymphadenopathy are not required

• Refractory or relapsed disease as evidenced by 1 of the following criteria:

  • Progression after ≥ 1 course of a purine nucleoside (i.e., fludarabine phosphate, cladribine, pentostatin) regimen
  • Progression after ≥ 1 course of an alkylator (i.e., cyclophosphamide or chlorambucil) regimen
  • Relapse after ≥ 1 prior purine nucleoside oral kylator (i.e., cyclophosphamide or chlorambucil) regimen

• Requires chemotherapy, as indicated by any of the following criteria:

  • Measurable (i.e., > 5,000/mm^3) and progressive clonal lymphocytosis
  • Measurable (i.e., single diameter > 2 cm) and progressive lymphadenopathy

  • Disease-related symptoms, including 1 or more of the following:

    • Weight loss > 10% within the past 6 months
    • Extreme fatigue attributed to CLL/SLL
    • Fevers > 100.5^oF for 2 weeks without evidence of infection
    • Night sweats without evidence of infection
  • Evidence of progressive marrow failure, as manifested by the development of or worsening anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelet count < 100,000/mm^3)
  • Massive (i.e. > 6 cm below left costal margin) or progressives plenomegaly
• No mantle cell lymphoma, as demonstrated by a negative fluorescent in situ hybridization (FISH) analysis fort(11;14)(IgVH/CCND1) on peripheral blood or tissue biopsy
• ECOG performance status 0-2
• Life expectancy ≥ 12 months
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min
• AST and ALT ≤ 2.5 times ULN
• Bilirubin normal
• Alkaline phosphatase ≤ 3 times ULN
• Platelet count > 30,000/mm^3 (without transfusion)
• Absolute neutrophil count > 1,000/mm^3
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to complete patient diaries alone or with assistance
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No other malignancy except for squamous cell or basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was curatively treated within the past 2 years
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate

• No inability to swallow or retain sunitinib malate capsules due to any of the following:

  • Gastrointestinal tract disease
  • Requirement for IV alimentation
  • Prior surgical procedures affecting absorption
  • Active peptic ulcer disease
• No pre-existing thyroid abnormality that would make the patient unable to maintain normal thyroid function with medication
• No pulmonary embolism within the past 12 months
• No serious or nonhealing wound, ulcer, or bone fracture

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infections
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No cerebrovascular accident or transient ischemic attack within the past 12 months
• No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)

• No significant cardiac arrhythmia, including any of the following:

  • QTc prolongation (i.e., QTc interval ≥ 500 msec)
  • Ventricular tachycardia
  • Atrial fibrillation
  • Atrial flutter
  • Second or third degree heart block

• No cardiac disease within the past 12 months, including any of the following:

  • Myocardial infarction
  • Cardiac arrhythmia
  • Stable/unstable angina
  • Symptomatic congestive heart failure
  • Coronary/peripheral artery bypass graft or stenting

• No New York Heart Association (NYHA) class III or IV heart failure

  • The following patients are eligible provided they have NYHA class II cardiac function on baseline ECHO/MUGA:

    • History of NYHA class II heart failure and asymptomatic on treatment
    • No prior anthracycline exposure
    • No prior central thoracic radiation that included the heart in the radiation port
• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• At least 4 weeks since prior rituximab or alemtuzumab
• At least 4 weeks since prior major surgery
• At least 4 weeks since prior oral steroids

• No prior treatment with any other antiangiogenic agent, including any of the following:

  • Bevacizumab
  • Sorafenib
  • Pazopanib
  • AZD2171
  • Vatalanib
  • VEGF Trap

• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

  • Ketoconazole
  • Itraconazole
  • Clarithromycin
  • Erythromycin
  • Diltiazem
  • Verapamil
  • HIV protease inhibitors (i.e., indinavir, saquinavir,ritonavir, atazanavir, nelfinavir)
  • Delavirdine

• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

  • Rifampin
  • Rifabutin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • Hypericum perforatum (St. John's wort)
  • Efavirenz
  • Tipranavir
• No other concurrent investigational agents

• No concurrent agents with proarrhythmic potential, including any of the following:

  • Terfenadine
  • Quinidine
  • Procainamide
  • Disopyramide
  • Sotalol
  • Probucol
  • Bepridil
  • Haloperidol
  • Risperidone
  • Indapamide
  • Flecainide
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies

• No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)

  • Concurrent prophylactic low molecular weight heparin or warfarin at doses ≤ 2 mg daily for thrombosis prophylaxis allowed