Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

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

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Secondary Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes
• Intervention / Treatment: Drug: sunitinib malate

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I; Patients will receive sunitinib malate (SU11248) by mouth once a day. Treatment may continue for as long as benefit is shown.	Drug: sunitinib malate; Given orally; Other Names: Sutent; SU11248; sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Karen Yee, University Health Network-Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): October 1, 2012

Study Registration Dates

• First Submitted: March 20, 2007
• First Submitted That Met QC Criteria: March 20, 2007
• First Posted (ESTIMATE): March 22, 2007

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: NCI-2009-00211; N01CM62203 (U.S. NIH Grant/Contract); PHL-063 (OTHER_GRANT: N01CM62203); CDR0000535656 (OTHER_GRANT: N01CM62203)