Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

This is an interventional treatment trial for Chronic Myelomonocytic Leukemia Read More

Inclusion Criteria:

• MDS syndromes meeting 1 of the following: Intermediate-2 disease, high-risk disease (IPSS score>=1.5)
• CMML: WBC>12,000/mm^3, Intermediate-2 disease with WBC=<12,000/mm^3, high-risk disease (IPSS score>=1.5) with WBC=<12,000/mm^3
• Patients with insufficient/inadequate metaphases for cytogenetic analysis are eligible if bone marrow blasts are >10% and/or 2-3 cytopenias are present
• No known brain metastases
• Life expectancy>12 weeks
• ECOG PS 0-2/Karnofsky PS 60-100%
• Calcium=<3.0 mmol/L
• Bilirubin normal
• AST and ALT=<2.5 times upper limit of normal
• Creatinine normal/creatinine clearance>=60 mL/min

Exclusion Criteria:

• No history of significant ECG abnormalities including but not limited to: ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation>=3 beats in a row); QTc prolongation (i.e.QTc interval>=500msec)
• No history of allergic reaction to compounds of similar chemical/biological composition to sunitinib malate
• No NYHA class III-IV congestive heart failure
• Patients with history of NYHA class II congestive heart failure who are asymptomatic on treatment are eligible
• No abdominal fistula/G perforation/intraabdominal abscess within past 28 days
• No serious cardiovascular disease within past 12 months including: cerebrovascular accident or transient ischemic attack, myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, coronary or peripheral artery bypass graft or stenting
• No pulmonary embolism within past 12 months
• No uncontrolled hypertension (systolic BP>=140 mmHg/diastolic BP>=90 mmHg)
• No condition impairing ability to swallow/retain sunitinib malate tablets including: GI tract disease resulting in inability to take oral medication, requirement for IV alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease
• No serious/nonhealing wound, ulcer, or bone fracture
• No uncontrolled pre-existing thyroid abnormality
• No concurrent uncontrolled illness including ongoing/active infection
• No psychiatric illness/social situation that would preclude study participation
• Not pregnant/nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• 4 weeks since prior major surgery
• Prior central thoracic radiotherapy that included heart in radiotherapy port allowed provided NYHA congestive heart failure=<class II
• Prior anthracycline exposure allowed provided NYHA congestive heart failure=<class II
• No other prior therapy for MDS/CMML except epoetin alfa, darbepoetin alfa, filgrastim or sargramostim
• At least 2 weeks since prior epoetin alfa
• At least 4 weeks since prior darbepoetin alfa
• No other prior antiangiogenic agents including but not limited to: bevacizumab, sorafenib tosylate, pazopanib hydrochloride, AZD2171, vatalanib, VEGF Trap
• More than 7 days since prior and no concurrent potent CYP3A4 inhibitors
• More than 12 days since prior and no concurrent potent CYP3A4 inducers including: Rifampin, Rifabutin, Carbamazepine, Phenobarbital, Phenytoin, Hypericum perforatum, Efavirenz, Tipranavir
• No concurrent birth control patch/oral birth control pills/depot/injectable birth control methods
• No concurrent therapeutic coumarin-derivative anticoagulants
• Low dose(=<2mg) warfarin for prophylaxis of thrombosis allowed
• Low molecular weight heparin allowed if INR=<1.5
• No concurrent agents with proarrhythmic potential including: Terfenadine, Quinidine, Procainamide, Disopyramide, Sotalol, Probucol, Bepridil, Haloperidol, Risperidone, Indapamide, Flecainide acetate
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents