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

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Low-dose Decitabine, Valproic acid, All-trans retinoic acid, Older Patients Read More

Inclusion Criteria:

1. Written informed consent obtained according to international guidelines and local law;
2. Male or female patients aged > 60 years without upper age limit;
3. Patients with primary or secondary AML according to WHO (≥ 20% blasts in the peripheral blood (pB) or bone marrow (BM)) who are not expected to benefit from standard remission-induction chemotherapy;
4. Patients with < 30 000 leukocytes/μl;
5. Performance status ECOG 0, 1, 2;
6. Creatinine < 2.0 mg/dl (unless leukemia-related);
7. Ability to understand the nature of the study and the study related procedures and to comply with them.

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);
8. Other malignancy requiring treatment (previous chemotherapy for other malignancies is not an exclusion criteria);
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.