Study of Sensitization of Non-M3 AML Blasts to ATRA by Epigenetic Treatment With Tranylcypromine (TCP)

Patients eligible for inclusion in this trial must meet all of the following criteria:

1. Patients >18 years (no upper age limit);
2. AML (WHO) or intermediate or higher risk MDS/ Chronic Myelomonocytic Leukemia (CMML) (IPSS-R >3.0);
3. No standard treatment available (comorbidities, higher age, refractoriness to standard or salvage chemotherapy and allografting, azanucleosides failure*);
4. Patients with \< 30.000 leukocytes/µl;
5. Eastern Cooperative Oncology Group (ECOG) 0,1,2;
6. Written informed consent obtained according to international guidelines and local laws;

7. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

   • Azanucleosides failure is defined as 1) no response after at least three (AML) or six (MDS) cycles of azacitidine or decitabine, 2) disease progression under treatment or 3) grade 3-4 non-hematologic toxicity.

Exclusion Criteria:

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

1. Acute promyelocytic leukemia (APL, French-American-British classification system (FAB) M3);
2. Eligibility for standard induction or consolidation chemotherapy, immediate allografting, or a hypomethylating agent;
3. AML with central nervous system (CNS) involvement;
4. AraC treatment within one month prior to registration;
5. Prior exposure to histone deacetylase inhibitors, including sodium valproate within one month prior to registration;
6. Stem cell transplant patient with graft-versus-host disease (GvHD) or under systemic immunosuppression;
7. Previous gastrointestinal surgery that might interfere with drug absorption;
8. Pheochromocytoma;
9. Carcinoid tumor;
10. Confirmed or suspected cerebrovascular disease;
11. Vascular malformations including aneurysm;
12. Severe renal insufficiency;
13. Severe or poorly controlled hypertension;
14. Severe cardiovascular disease;
15. Hepatic insufficiency/liver disease;
16. Porphyria;
17. Diabetes insipidus;
18. History or presence of malignant hyperthermia;
19. Known psychiatric disorders;
20. Known allergy against soy beans or peanuts;
21. Known hypersensitivity to or intolerance of one of the trial drugs or its constituents (e.g. lactose, corn starch, indigocarmine (TCP), corn starch (AraC), other retinoids (ATRA));
22. Simultaneous intake of the prohibited medication, incl. linezolid, that is likely to cause interactions (see detailed list study protocol);
23. Patients who refuse to follow study-specific dietary guidelines;
24. Known or persistent abuse of medication, drugs or alcohol;
25. Current or planned pregnancy, nursing period;
26. Failure to use safe methods of contraception;
27. Simultaneous participation in other interventional trials which could interfere with this trial and/or participation before the end of a required restriction period;
28. Participation in a clinical trial within the last 30 days before the start of this trial
29. Persons who are in a relationship of dependence/employment with the sponsor or the investigator;