A Phase II Study of Sunitinib Malate for Treatment of Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
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