Clinical Study of SU 11248 (Sutent) Combined With Standard Chemotherapy in Patients With FLT3 Mutated AML Over 60 Years

Study Overview
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Brief Summary
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In this study safety and tolerability of two dose levels of SU 11248 (sutent) with standard chemotherapy in patients with FLT3 mutated AML over 60 years will be evaluated.

Official Title
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Phase I/II Clinical Study of SU11248 (Sutent) Combined With Standard Chemotherapy With Cytosine Arabinoside and Daunorubicin in Patients With FLT3 Mutated AML Over 60 Years of Age

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary or secondary acute myeloid leukemia (any FAB type, except M3). No prior systemic chemotherapy for AML except hydroxyurea. Cytoreductive therapy with hydroxyurea is recommended if WBC is > 50.000/µl, but should cease at least one day prior to starting study medication Patient age equal or of greater than 60 years Patients must have FLT3 mutated AML, either ITD or kinase domain mutations ECOG Performance score 3 or less (Karnofsky Performance Score >40%). Life expectancy more than four weeks. Adequate hepatic and renal function, as defined by serum transaminases <2.5x ULN, bilirubin <1.5x ULN. Creatinine <1.5x ULN. Patients must provide written informed consent to participate in the trial. Normal heart function on cardiac ultrasound Prothrombin time (PT) and partial thromboplastin time (PTT) <=1.5 x ULN Serum albumin >=3.0 g/dl Serum amylase and lipase <=1.0 x ULN Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: The presence of any of the following will exclude a subject from study enrollment: Treatment with any investigational agent within four weeks. Known HIV infection Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to: Presence of CNS leukaemia Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event. Current treatment with therapeutic doses of anticoagulant (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). Pre existing thyroid abnormality of thyroid function that cannot be maintained in the normal range with medication. Ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of any Grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sunitinib|25 mg or 37,5 mg daily dose until DLT|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Definition of a recommended Phase III dose and determination CTC version 3.0 grade 3-5 non-hematological toxicities of SU11248 in combination with standard induction and consolidation chemotherapy |  | April 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall safety profile of SU11248 characterized by type, frequency, severity (graded using NCI CTCAE Version 3.0), timing and relatedness of adverse events (AEs) and laboratory |  | April 2011 | 
| Objective tumor response, as defined using the revised recommendations of the International Working Group for diagnosis, standardization of response criteria in Acute Myeloid Leukemia for AML |  | April 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, FLT3, acute myeloid leukemia, FLT 3 inhibitor, FLT3 mutated AML