Study of Decitabine Alone or in Combination With Valproic Acid and All-trans Retinoic Acid in Acute Myeloid Leukemia

Exclusion Criteria

• •1. AML of FAB subtype M3;
• •2. Previous remission-induction chemotherapy for MDS or AML, previous allografting;
• •3. Previous treatment with DAC, 5-azacytidine, VPA or another HDAC inhibitor, or ATRA;
• •4. "Low-dose" chemotherapy (e.g. hydroxyurea, cytosine arabinoside (Ara-C), melphalan, clofarabine etc.) within 4 weeks prior to DAC treatment, except for cytoreduction of leukocytosis ≥ 30 000/μl with hydroxyurea or Ara-C as proscribed by the study protocol (section 7.3 and 7.4); the patient must have recovered from all clinically relevant reversible non-hematologic toxicities;
• •5. Treatment with tyrosine kinase inhibitors, immunomodulating agents (IMIDS) or other investigational AML treatment within the last 4 weeks or in a time period of drug half-life x 5 (whatever is shorter) before the first administration of DAC;
• •6. Treatment with cytokines within previous 4 weeks;
• •7. Concomitant therapy which is considered relevant for the evaluation of efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy);
• •9. Cardiac insufficiency NYHA IV;
• •10. Insufficient hepatic function (bilirubin, AST or ALT \> = 2.5 x Upper Limit of Normal (ULN)) (unless leukemia-related);
• •11. Fatal hepatic function disorder during treatment with valproic acid in siblings;
• •12. Hepatic porphyria;
• •13. Manifest serious pancreatic function disorder;
• •14. Plasmatic coagulation disorder not related to AML;
• •15. Known active hepatitis B or C;
• •16. Known HIV infection;
• •17. Other uncontrolled active infections;
• •18. Known allergy against soy beans or peanuts;
• •19. Psychiatric disorder that interferes with treatment;
• •20. Patient without legal capacity who is unable to understand the nature, significance and consequences of the study;
• •21. Known hypersensitivity to, or intolerance of, one of the trial drugs, another retinoid or the excipients of the trial drugs;
• •22. Concomitant use of any other investigational drug or participation in a clinical trial within the last thirty days before the start of this study; simultaneous participation in registry and diagnostic trials is allowed;
• •23. Female patients who are pregnant or breast feeding;
• •24. Fertile patients refusing to use safe contraceptive methods during the study (for details see clinical trial protocol section 5.3);
• •25. Known or persistent abuse of medication, drugs or alcohol.