Clinical trial NCT00783653: Clinical Study of SU 11248 (Sutent) Combined With Standard Chemotherapy in Patients With FLT3 Mutated AML Over 60 Years
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
FLT3
acute myeloid leukemia
FLT 3 inhibitor
FLT3 mutated AML
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2008-11-02
Enrollment: 22
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: April 2011
Secondary outcomes:
measure: 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
timeFrame: April 2011
measure: 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
timeFrame: April 2011
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: Prof. Dr. med. Walter Fiedler
city: Hannover
country: Germany
facility: PD Dr. med. Jürgen Krauter
city: München
country: Germany
facility: Dr. Katharina Götze
city: Tübingen
country: Germany
facility: Prof. Dr. Helmut R. Salih
city: Ulm
country: Germany
facility: Dr. Richard Schlenk
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Walter Fiedler
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fiedler W, Kayser S, Kebenko M, Janning M, Krauter J, Schittenhelm M, Gotze K, Weber D, Gohring G, Teleanu V, Thol F, Heuser M, Dohner K, Ganser A, Dohner H, Schlenk RF. A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations. Br J Haematol. 2015 Jun;169(5):694-700. doi: 10.1111/bjh.13353. Epub 2015 Mar 29.