Clinical trial NCT01130662 (phase 1, status: completed)
Conditions: acute myeloid leukemia
ICD codes: C92.A1, C92.A2, C92.61, C92.62, C92.A0, C92.60
Drugs: combination therapy using decitabine and midostaurin
SMILES: NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1
Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 60 years of age with newly diagnosed AML that is not eligible for standard induction
             or ≥ 18 years of age with relapsed/refractory AML

          -  Histologically documented AML (except t(15;17)according to the World Health
             Association (WHO) criteria

          -  Karnofsky performance status ≥ 70

          -  Must have the following lab values:

          -  AST and ALT < or equal to 2.5 x Upper Limit of Normal (ULN)

          -  Serum Bilirubin < or equal to 2.5 x ULN

          -  Serum Creatinine < or equal to 2.5 x ULN

          -  Must give written informed consent

          -  Left ventricular ejection fraction ≥ 50%

        Exclusion Criteria:

          -  Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell
             transplant less than 2 months previously

          -  Uncontrolled active infection

          -  Known impairment of GI function or GI disease that may significantly alter the
             absorption of midostaurin

          -  Female patients who are pregnant or breast-feeding or adults of reproductive potential
             not using an effective method of birth control. Barrier contraceptives must be used
             throughout the study in both sexes. Women of childbearing potential must have a
             negative serum pregnancy test 48 hours prior to administration of midostaurin. Women
             considered not of childbearing potential include any of the following: no menses for
             at least 5 years or menses within 5 years but amenorrheic for at least 2 months and
             luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal
             range (according to definition of postmenopausal for laboratory used) or bilateral
             oophorectomy or radiation castration and amenorrheic for at least 3 months.

          -  Other known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled
             medical condition (eg 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.

          -  Impaired cardiac function including any of the following:

          -  Screening ECG with a QTc > 450 msec

          -  Congenital long QT syndrome

          -  History or presence of sustained ventricular tachycardia

          -  Any history of ventricular fibrillation or torsades de pointes

          -  Bradycardia defined as HR less than 50 bpm

          -  Right bundle branch block + left anterior hemiblock (bifascicular block)

          -  Myocardial infarction or unstable angina < 6 months prior to starting study drug

          -  CHF NY Heart Association class III or IV

          -  Ejection fraction < 50% assessed by MUGA or ECHO scan within 14 days of Day 1

          -  Known confirmed diagnosis of HIV infection or active viral hepatitis

          -  Received any investigational agent within 30 days prior to Day 1

          -  Any surgical procedure, excluding central venous catheter placement, bone marrow
             biopsy or other minor procedures (eg skin biopsy) within 14 days of Day 1

          -  Unwilling or unable to comply with the protocol

          -  Known malignant disease of the central nervous system

          -  Any pulmonary infiltrate including those suspected to be of infectious origin. In
             particular, patients with resolution of clinical symptoms of pulmonary infection but
             with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary
             infiltrates have completely resolved

          -  Patients with prior midostaurin (PKC412) treatment are excluded

          -  Patients receiving any other investigational agents or have received other
             investigational agents within 30 days of enrollment

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to midostaurin and/or decitabine