C92.0 D46.9
Conditions
Interventions
Group 1: Study treatment: TCP + ATRA + AraC
Four dose levels of TCP (20 mg, 40 mg, 60 mg, 80 mg on days 1-28) will be examined in combination with fixed dose ATRA (45 mg/m2 on days 10-28) and fixed-do
Sponsors
Universitätsklinikum Freiburg
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients >18 years (no upper age limit); 2. AML (WHO) or intermediate or higher risk MDS/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. 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
Exclusion criteria: Acute promyelocytic leukemia (APL, FAB M3); 2. Eligibility for standard induction or consolidation chemotherapy, immediate allografting, or a hypomethylating agent; 3. AML with 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 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, indigocarmin (TCP), corn starch (AraC), other retinoids (ATRA)); 22. Simultaneous intake of the prohibited medication, incl. linezolid, that is likely to cause interactions; 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the phase I part of the study is DLT in the first 28 days of treatment. DLT is defined as a toxicity that is considered by the investigator to be related to the combination TCP+ATRA or TCP+AraC+ATRA and necessitates to reduce the dose of the investigational product or to even stop treatment. The aim is the determination of the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D).The primary endpoint of the phase II part of the study is objective best response (CR, CRi, PR). | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety: - Adverse events and serious adverse events - Vital signs (pulse rate and blood pressure) - Laboratory data including hematologic parameters Efficacy (phase II part): - Overall survival - EORTC QLQ C30 - HADS-D Translational endpoints: - in vivo target validation and functional evaluation of LSD1 inhibition | — |
Countries
Germany
Contacts
Public ContactUlrike Kohlweyer
Universitätsklinikum Freiburg, Dept. Innere Medizin, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation
Outcome results
None listed