Decitabine and Midostaurin in Treating Older Patients with Newly Diagnosed Acute Myeloid Leukemia

Inclusion Criteria

• Newly diagnosed AML (according to 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) or other antecedent hematologic malignancy treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) (i.e., decitabine or azacitidine)
• Confirmed FLT3-ITD mutation, measured on peripheral blood or bone marrow aspirate prior to study enrollment (patients may also have a concurrent FLT3-tyrosine kinase domain [TKD] mutation)
• 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 x 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 of greater than two months

Exclusion Criteria

• Patients receiving concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea; however, prior treatment with DNMTi therapy (i.e., decitabine or azacitidine) for MDS or other antecedent hematologic malignancy is allowed * NOTE: if the patient has been initiated on the protocol defined regimen (i.e. decitabine without a FLT3 inhibitor) before the FLT3 mutation status was known, the patient may be registered on the protocol and start midostaurin on day 11
• Anti-neoplastic treatment less than 4 weeks prior to enrollment, with the exception of hydroxyurea
• Inability to swallow or absorb drug
• Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin
• A known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
• Patients who have received any investigational agent within 4 weeks of enrollment
• Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of day 1
• Unwillingness or inability to comply with the protocol
• Known active central nervous system (CNS) malignancy
• Previous or current history of a myeloproliferative disease
• 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 III or IV
• Any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and poorly controlled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study; 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
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• 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 include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been 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
• Sexually active males unless they use a condom during intercourse while taking drug and for 5 months after stopping midostaurin medication; they should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
• Combination of any two of the following: * Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception * 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 ** In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment