Sunitinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: B-cell Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: sunitinib malate; pharmacological study; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies; Correlative studies
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well sunitinib works in treating patients with relapsed
      or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. Sunitinib may stop
      the growth of cancer cells by blocking some of the enzymes needed for cell growth and by
      blocking blood flow to the cancer.
    

Eligibility criteria:

        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