Study of Decitabine Alone or in Combination With Valproic Acid and All-trans Retinoic Acid in Acute Myeloid Leukemia
Acute Myeloid Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
Acute Myeloid Leukemia, Low-dose Decitabine, Valproic acid, All-trans retinoic acid, Older Patients
Study Type
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Decitabine Type: Drug
Name: VPA Type: Drug
Name: ATRA Type: Drug
Overall Status
AML of the older patient constitutes a major unmet clinical need since the large majority will not be found eligible for induction chemotherapy. Reasons for this decision include host factors (comorbidities, reduced performance status, functional limitations due to age), leading to often poor tolerance of repeated chemotherapy courses and the unfavorable biology underlying this disease in older patients. Low dose Decitabine has shown very promising efficacy in high-risk MDS and is therefore a very promising approach also in older AML patients. Preliminary results from several centres have demonstrated excellent feasibility and good efficacy of this treatment. Therefore the investigators intend to investigate the effects of two drugs added onto low-dose Decitabine which have shown very promising synergistic effects in vitro and for which preliminary results indicate that the combination with low-dose Decitabine is very feasible.
Detailed Description
By employing a 2x2 factorial design, this phase II study will address the possible added efficacy of addition of one or even both of these agents to low-dose Decitabine. The primary endpoint of this study will be objective response rate (complete and partial remissions).
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 60 Years
Gender: Both
Criteria: 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.
Klinikum der Technischen Universität Aachen
Aachen, Germany
Status: Recruiting
Contact: Edgar Jost, MD -
Vivantes Klinikum Neukölln
Berlin, Germany
Status: Recruiting
Contact: Maike De Wit -
Augusta-Kranken-Anstalt gGmbH
Bochum, Germany
Status: Recruiting
Contact: Dirk Behringer -
Klinikum Braunschweig
Braunschweig, Germany
Status: Recruiting
Contact: Jürgen Krauter,
DIAKO Ev. Diakonie-Krankenhaus gGmbH
Bremen, Germany
Status: Recruiting
Contact: Johannes Kullmer, Dr. -
Marien Hospital Düsseldorf
Düsseldorf, Germany
Status: Recruiting
Contact: Aristoteles Giagounidis, PD, Dr. -
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
Status: Recruiting
Contact: Ulrich Germing, Prof. -
Klinikum Esslingen GmbH
Esslingen, Germany
Status: Recruiting
Contact: Carsten Schwänen, -
Universität Frankfurt
Frankfurt, Germany
Status: Recruiting
Contact: Gesine Bug -
Medizinische Universitätsklinik Freiburg
Freiburg, Germany
Status: Recruiting
Contact: Michael Lübbert, -
St. Marien-Hospital Hagen
Hagen, Germany
Status: Recruiting
Contact: H.-W. Lindemann, MD -
Universitätsklinikum Halle
Halle, Germany
Status: Active, not recruiting
Evangelisches Krankenhaus Hamm gGmbH
Hamm, Germany
Status: Recruiting
Contact: Elisabeth Lange, Dr. med. -
Med. Hochschule Hannover
Hannover, Germany
Status: Recruiting
Contact: A. Ganser, MD, PhD -
Universitätsklinikum Jena
Jena, Germany
Status: Recruiting
Contact: Sebastian Scholl -
Praxisklinik für Hämatologie und Onkologie Koblenz
Koblenz, Germany
Status: Active, not recruiting
Ortenau Klinikum Lahr-Ettenheim
Lahr, Germany
Status: Recruiting
Contact: Matthias Egger -
Caritas Krankenhaus Lebach
Lebach, Germany
Status: Recruiting
Contact: Stephan Kremers, -
Universitätsklinikum Leipzig AöR
Leipzig, Germany
Status: Recruiting
Contact: Dietger W. Niederwieser -
Klinikum Lüdenscheid
Lüdenscheid, Germany
Status: Recruiting
Contact: Gerhard Heil, -
Philipps-Universität Marburg
Marburg, Germany
Status: Recruiting
Contact: Andreas Neubauer -
TU München
München, Germany
Status: Recruiting
Contact: Katharina Götze, -
University of Münster Medical Center
Münster, Germany
Status: Recruiting
Contact: Stefanie Wiebe, -
Ortenau Klinikum
Offenburg, Germany
Status: Recruiting
Contact: Irmgard Dresel
Studienzentrum Onkologie Ravensburg
Ravensburg, Germany
Status: Recruiting
Contact: Tobias Dechow, -
Eberhard Karls Universität Tübingen
Tübingen, Germany
Status: Recruiting
Contact: Helmut Salih, -
Universitätsklinikum Ulm
Ulm, Germany
Status: Recruiting
Contact: Hartmut Döhner, -
Klinikum Villingen-Schwenningen
Villingen-Schwenningen, Germany
Status: Recruiting
Contact: Wolfram Brugger, Prof. -
Start Date
August 2011
Completion Date
December 2015
University Hospital Freiburg
University Hospital Freiburg
Record processing date processed this data on July 28, 2015 page