Midostaurin Access Program for Newly Diagnosed FLT3 (ITD or TKD) Mutated AML Adult Patients Eligible for Standard Induction and Consolidation Chemotherapy

An Open-label, Multi-center, Expanded Treatment Protocol of Midostaurin (PKC412) in Adult Patients With Newly Diagnosed Fms-like Tyrosine Kinase Receptor (FLT3) Mutated Acute Myeloid Leukemia (AML) Who Are Eligible for Standard Induction and Consolidation Chemotherapy.

The purpose of this study is to provide access to Midostaurin and gather additional safety data on the combination of Midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation chemotherapy.

The purpose of this study is to provide Midostaurin (study drug) treatment to newly diagnosed FLT3 mutated (ITD or TKD) AML adult patients (18 years or older) eligible for standard standard induction (cytarabine + daunorubicin/Idarubicin) and consolidation (cytarabine) chemotherapy.

Inclusion Criteria:

Written informed consent must be obtained prior to any screening procedures. Patients must meet all Inclusion Criteria:

• Patient is able to communicate well with the investigator, to understand and comply with the requirements of the study.
• Patients must be 18 years of age or older; elderly patients must be fit to receive intensive induction and consolidation chemotherapy
• Patients must have a documented FLT3 mutation (ITD or TKD)
• Patients must have an ECOG Performance Status of ≤ 2
• Patients must have a documented unequivocal diagnosis of AML according to WHO 2008 classification (>20% blasts in the bone marrow and/or peripheral blood), excluding M3 (acute promyelocytic leukemia).
• Patients requiring intrathecal chemotherapy must have a minimum washout of 48 hours prior to the first dose of midostaurin
• AML patients with a history of antecedent treatment for myelodysplasia (MDS), e.g. azacitidine or decitabine, remain eligible for treatment on this study. These agents must have been discontinued for a period of at least 30 days or 5 half-lives of the drug (whichever is greater) before midostaurin can be administered.
• Secondary AML, e.g. patients with antecedent history of treatment for prior malignancy Patients must have the following laboratory values (Direct Bilirubin ≤ 2.5 x ULN, Serum Creatinine ≤ 2.5 x ULN)

Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria:

• Prior therapy for AML with the following exceptions: (emergency leukapheresis, emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 5 days, cranial RT for CNS leukostasis (one dose only), growth factor/cytokine support)
• Patients with LVEF less than 45% (by echocardiogram or MUGA) or symptomatic congestive heart failure, Class III or IV according to New York Heart Association (NYHA) classification
• Patients with any uncontrolled illness, including, but not limited to, acute or chronic pancreatitis or uncontrolled infection
• QTc >500 msec on screening ECG. History of hypersensitivity to any drugs or metabolites of similar chemical classes as the IMP.
• Participation in a prior investigational interventional (drug) study with administration of the investigational product within 30 days or 5 half-lives of the investigational product, whichever is longer.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.
• Sexually active males should not father a child during this study and for upto 5 months following.