decitabine and midostaurin in treating older patients with newly diagnosed acute myeloid leukemia

Conditions: Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults; AML (Adult) With 11q23 (MLL) Abnormalities; AML (Adult) With Del (5q); AML (Adult) With Inv (16) (p13; q22); AML (Adult) With t (16;16) (p13; q22); AML (Adult) With t (8; 21) (q22; q22); Secondary AML (Adult); Untreated AML (Adult)

Summary: this phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (aml) in older patients.

treatment with decitabine, a cytidine analog, then midostaurin, a multi-target protein kinase inhibitor (pki), may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Eligibility criteria:
inclusion criteria: * newly-diagnosed acute myeloid leukemia (aml) per the world health organization \[who\] 2008 classification \[except t (15; 17)\], including: * de novo aml * secondary aml * secondary aml arising from previously-diagnosed myelodysplastic syndromes (mds) treated with deoxyribonucleic acid (dna) methyltransferase inhibitor (dnmti) (ie, decitabine or azacitidine) * flt3-itd mutation confirmed in bone marrow aspirate * eastern cooperative oncology group (ecog) performance status ≤ 2 * aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 2.5 x upper limit of normal (uln) * serum bilirubin ≤ 2.5 uln * serum creatinine ≤ 1.5 mg/dl and/or creatinine clearance ≥ 50 ml/min * ejection fraction ≥ 50% by echocardiogram * unwillingness or inability to receive conventional chemotherapy * ability to understand and the willingness to sign a written informed consent document * ability to adhere to the study visit schedule and other protocol requirements * life expectancy \> 2 months exclusion criteria: * receiving concomitant treatment with other anti-neoplastic agents (exception: hydroxyurea). prior treatment with dnmti therapy (ie, decitabine or azacitidine) for mds is allowed * received anti-neoplastic treatment within 4 weeks prior to enrollment (exception: hydroxyurea) * received any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of study day 1 * received any investigational agent within 4 weeks prior to enrollment * previous or current history of a myeloproliferative disease * known active central nervous system (cns) malignancy * any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition which could compromise participation in the study (eg, uncontrolled diabetes; cardiovascular disease including congestive heart failure; myocardial infarction within 6 months with poorly controlled hypertension; chronic renal disease; active uncontrolled infection) * active opportunistic infection or treatment for opportunistic infection within 4 weeks of first day of study drug dosing * known confirmed diagnosis of human immunodeficiency virus (hiv) infection or active viral hepatitis * known impairment of gastrointestinal (gi) function or gi disease that may significantly alter the absorption of midostaurin * history of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine * impaired cardiac function including any of the following: * screening electrocardiogram (ecg) with a corrected qt interval (qtc) \> 450 msec * bradycardia defined as heart rate (hr) \< 50 beats per minute (bpm) * right bundle branch block + left anterior hemiblock (bifascicular block) * patients with myocardial infarction or unstable angina \< 3 months prior to starting study drug * congestive heart failure (chf) new york (ny) heart association class 3 or 4 * inability to swallow or absorb drug * other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation * unwillingness or inability to comply with the protocol * pregnant * nursing (lactating) * women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after midostaurin medication; highly effective contraception methods as follows: * total abstinence, when this is in line with the preferred and usual lifestyle of the subject \[periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\] * female sterilization (surgical bilateral oophorectomy with or without hysterectomy; or tubal ligation at least six weeks before taking study treatment). in case of oophorectomy alone, reproductive status must be confirmed by follow-up hormone level assessment * male sterilization, at least 6 months prior to screening (for female subjects on the study, the vasectomized male partner should be the sole partner for that subject) * combination of any two of the following (a+b or a+c, or b+c): * use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), eg, hormone vaginal ring or transdermal hormone contraception. for oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment * placement of an intrauterine device (iud) or intrauterine system (ius) * barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository