Clinical trial NCT00398112 (phase 2, status: completed)
Conditions: b-cell chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia
ICD codes: C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, A87.2, K52.832, D72.111, C91.11, C91.12, C91.10
Drugs: sunitinib malate
SMILES: CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C
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