Sunitinib in Treating Patients With Idiopathic Myelofibrosis
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Hairy Cell Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Hairy Cell; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Leukemia, Prolymphocytic; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Large Granular Lymphocytic; Leukemia, Mast-Cell; Primary Myelofibrosis; Recurrence
Intervention: sunitinib malate
Intervention description: Given PO
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well sunitinib works in treating patients with idiopathic
      myelofibrosis. Sunitinib may stop the growth of abnormal cells by blocking some of the
      enzymes needed for cell growth and by blocking blood flow to the abnormal cells.
    

Eligibility criteria:

        Criteria:

          -  At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or
             mitomycin C)

          -  At least 4 weeks since prior major surgery

          -  At least 7 days since prior and no concurrent CYP3A4 inhibitors, including azole
             antifungals (ketoconazole and itraconazole), clarithromycin, erythromycin, diltiazem,
             verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,
             nelfinavir), and delavirdine

          -  At least 12 days since prior and no concurrent CYP3A4 inducers, including rifampin,
             rifabutin, carbamazepine, phenobarbital, phenytoin, Hypericum perforatum (St. John's
             wort), efavirenz, and tipranavir

          -  No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171,
             vatalanib, VEGF Trap)

          -  No other concurrent investigational agents

          -  No other concurrent anticancer agents or therapies

          -  No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)
             (Warfarin =< 2 mg/day for prophylaxis of thrombosis and low molecular weight heparin
             allowed provided INR =< 1.5)

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine,
             procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone,
             indapamide, and flecainide)

        Inclusion Criteria:

          -  Diagnosis of MF (histologically confirmed) requiring therapy, including those
             previously treated and relapsed or refractory (no more than one prior standard acute
             leukemia-type chemotherapy regimen; no limit on prior MF - directed therapies) or if
             newly diagnosed, with intermediate or high risk according to Lille scoring system
             (adverse prognostic factors are: Hb < 10 g/dl, WBC < 4 or > 30 x 10^9/L; risk group: 0
             = low, 1 = intermediate, 2 = high), or with symptomatic organomegaly.

          -  Serum bilirubin levels </= 2x upper limit of the normal (ULN). Higher levels are
             acceptable if these can be attributed to active hemolysis or MF

          -  Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels </=
             2x ULN. Higher levels are acceptable if these can be attributed to MF.

          -  Serum creatinine levels </= 2x ULN.

          -  Eighteen years of age or older.

          -  ECOG performance status 0-1 (Karnofsky </= 70%).

          -  Patients must have QTc < 500 msec

          -  Women of childbearing potential and men must agree to use adequate contraception (e.g.
             hormonal or barrier method of birth control; abstinence) for the duration of study
             participation. All women of childbearing potential must have a negative pregnancy test
             prior to receiving sunitinib. 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 document

          -  Both men and women and members of all races and ethnic groups are eligible for this
             trial.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to beginning treatment or those who have not
             recovered from treatment-limiting adverse events (to grade 1 or better) due to agents
             administered more than 4 weeks earlier. At least 4 weeks must have elapsed since any
             major surgery prior to study enrollment. Continuous use of supportive care medications
             (i. e. growth factors, anagrelide, or hydroxyurea) is allowed.

          -  Patients may not be receiving any other investigational agents.

          -  Patients who have received prior treatment with any other specific antiangiogenic
             agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, VEGF Trap, etc.)
             targeting VEGF/VEGFR system. Other agents that may have some antiangiogenic effects
             are allowed). (i.e. thalidomide)

          -  Patients with abnormal QTc prolongation (defined as a QTc interval equal to or greater
             than 500 msec) or patients who have a history of serious ventricular arrhythmia (VT or
             VF>/= 3 beats in a row or other significant (as judged by treating physician) ECG
             abnormalities.Patients with consistently poorly controlled (during the month prior to
             study screening) hypertension (systolic blood pressure of 140 mmHg or higher or
             diastolic blood pressure of 90 mmHg or higher) despite appropriate medical management
             of the hypertension.

          -  Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
             such as warfarin. Exceptions include: patients using warfarin of up to 2 mg daily for
             prophylaxis of thrombosis, and patients using low molecular weight heparin provided
             the patient's INR is </= 1.5.

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for IV alimentation, prior surgical
             procedures affecting absorption, or active peptic ulcer disease) that impairs their
             ability to swallow and retain sunitinib tablets.

          -  Patients with any of the following conditions:·Serious or non-healing wound, ulcer, or
             bone fracture, history of abdominal fistula, gastrointestinal perforation, or
             intra-abdominal abscess within 28 days of treatment,·cerebrovascular accident (CVA) or
             transient ischemic attack, myocardial infarction, cardiac arrhythmia, stable/unstable
             angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass
             graft or stenting, or pulmonary embolism within 12 months prior to study,·Class III or
             IV heart failure as defined by the NYHA functional classification system.

          -  Because sunitinib is metabolized primarily by the CYP3A4 liver enzyme, the eligibility
             of patients taking medications that are potent inducers or inhibitors of that enzyme
             will be determined following a review of their case by the Principal Investigator.
             Every effort should be made to switch patients taking such agents or substances to
             other medications.

          -  Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid
             function in the normal range with medications.

          -  Patients with uncontrolled intercurrent illness (as judged by treating physician)
             including, but not limited to, ongoing or active infections requiring IV antibiotics.

          -  Pregnant women are excluded from this study because sunitinib is an antiangiogenic
             agent with the potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with sunitinib, breastfeeding should be discontinued if the
             mother is treated with sunitinib malate.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with sunitinib. In addition, these
             patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated.