Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00451048
• Other study ID #: NCI-2009-00211
• Secondary ID: PHL-063CDR000053
• Status: Completed
• Phase: Phase 2
• Start date: February 2007
• Est. completion date: October 2012

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndromes
• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Preleukemia
• Secondary Myelodysplastic Syndromes
• Syndrome

Intervention

Drug:
• sunitinib malate
Given orally

Locations

Country	Name	City	State
Canada	London Regional Cancer Program	London	Ontario
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (Complete Response, Partial Response, or Hematologic Improvement) Defined by the International Working Group Criteria		Up to 6 years
Secondary	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
Secondary	Overall Survival		At 6 months and 1 year
Secondary	Progression-free Survival		At 6 months and 1 year
Secondary	Time to Progression		At 6 months and 1 year
Secondary	Highest Severity of Observed Adverse Events Assessed by Common Terminology Criteria or Adverse Events Version 3.0 (CTCAE v3.0)		Up to 6 years