Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Study Overview
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Brief Summary
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This phase II trial is studying how well sunitinib works in treating patients with myelodysplastic syndromes or chronic myelomonocytic leukemia. Sunitinib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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OBJECTIVES: I. Determine the overall response rate (complete response, partial response, or hematological improvement) in patients with intermediate-2 or high-risk myelodysplastic syndromes or chronic myelomonocytic leukemia treated with sunitinib malate. II. Determine the duration of response in patients treated with this drug. III. Determine the overall survival of patients treated with this drug. IV. Determine the progression-free survival of patients treated with this drug. V. Determine the time to disease progression in patients treated with this drug. VI. Determine the toxicity of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3-4 weeks and then monthly thereafter.

Official Title
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A Phase II Study of Sunitinib Malate (Sutent®; SU11248) in Patients With Intermediate-2 or High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Conditions
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Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients will receive sunitinib malate (SU11248) by mouth once a day. Treatment may continue for as long as benefit is shown. | Drug: sunitinib malate<br>* Given orally<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (Complete Response, Partial Response, or Hematologic Improvement) Defined by the International Working Group Criteria |  | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Participants With Complete, Partial or Hematologic Improvement Response | Assessed by achievement of Complete Response (CR), Partial Response (PR) or Hematologic Improvement (HI) | Up to 6 years | 
| Overall Survival |  | At 6 months and 1 year | 
| Progression-free Survival |  | At 6 months and 1 year | 
| Time to Progression |  | At 6 months and 1 year | 
| Highest Severity of Observed Adverse Events Assessed by Common Terminology Criteria or Adverse Events Version 3.0 (CTCAE v3.0) |  | Up to 6 years |