Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Phase 2

Completed

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

Interventions: Drug: sunitinib malate

Registration Number: NCT00451048

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	sunitinib malate	Patients will receive sunitinib malate (SU11248) by mouth once a day. Treatment may continue for as long as benefit is shown.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (Complete Response, Partial Response, or Hematologic Improvement) Defined by the International Working Group Criteria	Up to 6 years

Secondary Outcome Measures

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

Trial Locations

Locations (4): Odette Cancer Centre- Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
University Health Network-Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
London Regional Cancer Program
🇨🇦
London, Ontario, Canada