Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations

Exclusion Criteria

• •The presence of any of the following will exclude a patient from study enrollment:
• •1. Known or suspected hypersensitivity to the study drugs and/or any excipients
• •2. ECOG performance status \>2
• •3. Inadequate cardiac, hepatic and/or renal function at the Screening Visit defined as:
• •* ejection fraction \< 45% confirmed by echocardiography
• •* creatinine \>1.5x upper normal serum level
• •* total bilirubin \> upper normal serum level
• •* AST or ALT \>2x upper normal serum level
• •4. Active central nervous system involvement
• •5. Any clinically significant, advanced or unstable disease or history of that may interfere with primary or secondary variable evaluations or put the patient at special risk, such as:
• •* Myocardial infarction, unstable angina within 3 months before screening
• •* Heart failure NYHA III/IV
• •* Severe obstructive or restrictive ventilation disorder
• •* Uncontrolled infection
• •6. Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
• •7. Currently receiving a therapy not permitted during the study, as defined in Section 10.6.5
• •8. Active Graft-versus-Host Disease (GvHD) under immunosuppressive therapy different from steroids
• •9. Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.
• •10. Pre-existing liver disease (e.g.,. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
• •11. Known history of positive test for hepatitis B surface antigen (HsbAg) or hepatitis C antibody or history of positive test for Human Immunodeficiency Virus (HIV)
• •12. Hematologic disorder independent of leukemia
• •13. No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician and/or other physicians involved in the treatment of the patient about study participation
• •14. No consent for biobanking
• •15. Current participation in any other interventional clinical study within 30 days before the first administration of the investigational product or at any time during the study
• •16. Patients known or suspected of not being able to comply with this trial protocol
• •17. Breast feeding women or women with a positive pregnancy test at Screening visit
• •18. Patients of childbearing potential not willing to use adequate contraception during study and 3 months after last dose of crenolanib.