Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

• Register: ClinicalTrials.gov
• Last refreshed on: 13 May 2013
• Main ID: NCT00451048
• Date of registration: 20/03/2007
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia
• Scientific title: A Phase II Study of Sunitinib Malate (Sutent®; SU11248) in Patients With Intermediate-2 or High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
• Date of first enrolment: February 2007
• Target sample size: 32
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00451048
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Canada, United States

Contacts

• Name: Karen Yee
• Affiliation: University Health Network-Princess Margaret Hospital

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Myelomonocytic Leukemia

de Novo Myelodysplastic Syndromes

Myelodysplastic Syndromes

Secondary Myelodysplastic Syndromes

Intervention(s)

Drug: sunitinib malate

Primary Outcome(s)

Overall response rate (complete response, partial response, or hematologic improvement) defined by the International Working Group Criteria [Time Frame: Up to 6 years]

Secondary Outcome(s)

Duration of response [Time Frame: Up to 6 years]

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]

Overall survival [Time Frame: At 6 months and 1 year]

Progression-free survival [Time Frame: At 6 months and 1 year]

Time to progression [Time Frame: At 6 months and 1 year]

Secondary ID(s)

CDR0000535656

N01CM62203

NCI-2009-00211

PHL-063

Source(s) of Monetary Support

Please refer to primary and secondary sponsors