A Phase II Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive 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)
treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi)
(i.e., decitabine or azacitidine)

- Confirmed FLT3-ITD or FLT3-TKD mutation, measured on bone marrow aspirate as part of
screening prior to study enrollment; sample will be submitted to Stanford clinical
lab and sent out for commercially available test at Laboratory for Personalized
Molecular Medicine

- 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 is allowed

- 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

- 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

- 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

- 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

- A known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active
viral hepatitis because of uncertain toxicity profile of midostaurin in this patient
population

- 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

- 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

- 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%), 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