Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00451048
First received: March 20, 2007
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndromes
Myelodysplastic Syndromes
Secondary Myelodysplastic Syndromes
Drug: sunitinib malate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response rate (complete response, partial response, or hematologic improvement) defined by the International Working Group Criteria [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At 6 months and 1 year ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: At 6 months and 1 year ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: At 6 months and 1 year ] [ Designated as safety issue: No ]
  • Frequency and severity of observed adverse events assessed by Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: February 2007
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown.
Drug: sunitinib malate
Given orally
Other Names:
  • SU11248
  • sunitinib
  • Sutent

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Myelodysplastic syndromes (MDS) meeting 1 of the following criteria: Intermediate-2 disease, high-risk disease (International Prognostic Scoring System [IPSS] score >= 1.5)
  • Chronic myelomonocytic leukemia (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 or inadequate metaphases for cytogenetic analysis are eligible provided bone marrow blasts are > 10% and/or 2-3 cytopenias are present
  • No known brain metastases
  • Life expectancy > 12 weeks
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Calcium =< 3.0 mmol/L
  • Bilirubin normal
  • AST and ALT =< 2.5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • No history of significant electrocardiogram abnormalities including, but not limited to, the following: ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation >= 3 beats in a row); QTc prolongation (i.e., QTc interval >= 500 msec)
  • No history of allergic reaction to compounds of similar chemical or biological composition to sunitinib malate
  • No NYHA class III-IV congestive heart failure
  • Patients with a history of NYHA class II congestive heart failure who are asymptomatic on treatment are eligible
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No serious cardiovascular disease within the past 12 months, including the following: 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 the past 12 months
  • No uncontrolled hypertension, defined as systolic blood pressure (BP) >= 140 mm Hg or diastolic BP >= 90 mm Hg
  • No condition that impairs the ability to swallow and retain sunitinib malate tablets, including the following: gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No uncontrolled pre-existing thyroid abnormality
  • No concurrent uncontrolled illness, including ongoing or active infection
  • No psychiatric illness or social situation that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception
  • At least 4 weeks since prior major surgery
  • Prior central thoracic radiotherapy that included the heart in the radiotherapy port allowed provided New York Heart Association (NYHA) congestive heart failure =< class II
  • Prior anthracycline exposure allowed provided NYHA congestive heart failure =< class II
  • No other prior therapy for MDS or CMML except for epoetin alfa, darbepoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
  • 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, the following: bevacizumab, sorafenib tosylate, pazopanib hydrochloride, AZD2171, vatalanib, VEGF Trap
  • More than 7 days since prior and no concurrent potent CYP3A4 inhibitors, including the following: azole antifungals (e.g., ketoconazole or itraconazole), HIV protease inhibitors (e.g., indinavir sulfate, saquinavir mesylate, ritonavir, atazanavir, or nelfinavir mesylate), verapamil, clarithromycin, erythromycin, diltiazem hydrochloride, delavirdine
  • More than 12 days since prior and no concurrent potent CYP3A4 inducers, including the following: Rifampin, Rifabutin, Carbamazepine, Phenobarbital, Phenytoin, Hypericum perforatum (St. John's wort), Efavirenz, Tipranavir
  • No concurrent birth control patch, oral birth control pills, depot, or injectable birth control methods
  • No concurrent therapeutic coumarin-derivative anticoagulants (e.g., warfarin)
  • Low dose (=< 2 mg) warfarin for prophylaxis of thrombosis allowed
  • Low molecular weight heparin allowed provided INR =< 1.5
  • No concurrent agents with proarrhythmic potential, including the following: 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00451048

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Karen Yee University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00451048     History of Changes
Other Study ID Numbers: NCI-2009-00211, PHL-063, CDR0000535656, N01CM62203
Study First Received: March 20, 2007
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014