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

Information source: University Hospital Freiburg
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Myeloid Leukemia

Intervention: Decitabine (Drug); VPA (Drug); ATRA (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University Hospital Freiburg

Official(s) and/or principal investigator(s):
Michael Lübbert, MD, PhD, Principal Investigator, Affiliation: Department of Hematology/Oncology, University of Freiburg Medical Center

Overall contact:
Björn Hackanson, MD, Phone: +49761270, Ext: 35340, Email: bjoern.hackanson@uniklinik-freiburg.de


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.

Clinical Details

Official title: Prospective Randomized Multicenter Phase II Trial of Low-dose Decitabine (DAC) Administered Alone or in Combination With the Histone Deacetylase Inhibitor Valproic Acid (VPA) and All-trans Retinoic Acid (ATRA) in Patients > 60 Years With Acute Myeloid Leukemia Who Are Ineligible for Induction Chemotherapy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Objective best response rate (complete remission (CR) and partial remission (PR))

Secondary outcome:

Overall best response rate (CR, PR and antileukemic effect (ALE))

progression-free survival (PFS)

overall survival (OS)

quality of life

safety and toxicity

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).


Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.


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.

Locations and Contacts

Björn Hackanson, MD, Phone: +49761270, Ext: 35340, Email: bjoern.hackanson@uniklinik-freiburg.de

Klinikum der Technischen Universität Aachen, Aachen 52074, Germany; Recruiting
Edgar Jost, MD, Email: ejost@ukaachen.de
Christian Hasenbank, Email: chasenbank@ukaachen.de
Edgar Jost, PD Dr., Principal Investigator

Vivantes Klinikum Neukölln, Berlin 12351, Germany; Recruiting
Maike De Wit, Email: maike.dewit@vivantes.de
Maike De Wit, Prof. Dr., Principal Investigator

Augusta-Kranken-Anstalt gGmbH, Bochum 44791, Germany; Recruiting
Dirk Behringer, Email: behringer@augusta-bochum.de
Dirk Behringer, Prof.Dr.med., Principal Investigator

Klinikum Braunschweig, Braunschweig 38126, Germany; Recruiting
Jürgen Krauter, Prof.Dr.med.
Jürgen Krauter, Prof.Dr.med., Principal Investigator

DIAKO Ev. Diakonie-Krankenhaus gGmbH, Bremen 28239, Germany; Recruiting
Johannes Kullmer, Dr., Email: j.kullmer@diako-bremen.de
Johannes Kullmer, Dr., Principal Investigator

Marien Hospital Düsseldorf, Düsseldorf 40479, Germany; Recruiting
Aristoteles Giagounidis, PD, Dr., Email: aristoteles.giagounidis@vkkd-kliniken.de
Linda Heinze, Email: linda.heinze@vkkd-kliniken.de
Aristeles Giagounidis, PD Dr., Principal Investigator

Universitätsklinikum Düsseldorf, Düsseldorf 40225, Germany; Recruiting
Ulrich Germing, Prof., Email: germing@med.uni-duesseldorf.de
U. Spiegelberg, Email: spiegelberg@med.uni-duesseldorf.de
U. Germing, Prof.Dr.med., Principal Investigator

Klinikum Esslingen GmbH, Esslingen 73730, Germany; Recruiting
Carsten Schwänen, Dr.med., Email: c.schwaenen@klinikum-esslingen.de
Rita Wiesner, Email: r.wiesner@klinikum-esslingen.de
Carsten Schwänen, Dr.med., Principal Investigator

Universität Frankfurt, Frankfurt, Germany; Recruiting
Gesine Bug, Email: g.bug@em.uni-frankfurt.de
Gesine Bug, PD Dr., Principal Investigator

Medizinische Universitätsklinik Freiburg, Freiburg 79106, Germany; Recruiting
Michael Lübbert, Prof.Dr.med., Email: michael.luebbert@uniklinik-freiburg.de
Michael Lübbert, Prof.Dr.med., Principal Investigator

St. Marien-Hospital Hagen, Hagen 58095, Germany; Recruiting
H.-W. Lindemann, MD, Email: w.lindemann@kkh-hagen.de
H.-W. Lindemann, Dr.med., Principal Investigator

Universitätsklinikum Halle, Halle 06120, Germany; Active, not recruiting

Evangelisches Krankenhaus Hamm gGmbH, Hamm 59063, Germany; Recruiting
Elisabeth Lange, Dr. med., Email: elange@evkhamm.de
beate Perschke, Email: bperschke@evkhamm.de
Elisabeth Lange, Dr.med., Principal Investigator

Med. Hochschule Hannover, Hannover 30625, Germany; Recruiting
A. Ganser, MD, PhD, Email: haematologie.onkologie@mh-hannover.de
A. Ganser, Prof.Dr.med., Principal Investigator

Universitätsklinikum Jena, Jena 07747, Germany; Recruiting
Sebastian Scholl, Email: sebastian.scholl@med.uni-jena.de
Sebastian Scholl, PD Dr., Principal Investigator

Praxisklinik für Hämatologie und Onkologie Koblenz, Koblenz 56065, Germany; Active, not recruiting

Ortenau Klinikum Lahr-Ettenheim, Lahr 77933, Germany; Recruiting
Matthias Egger, Email: matthias.egger@le.ortenau-klinikum.de
Matthias Egger, Dr. med., Principal Investigator

Caritas Krankenhaus Lebach, Lebach 66822, Germany; Recruiting
Stephan Kremers, Dr.med., Email: s.kremers@caritas-krankenhaus-lebach.de
Stephan Kremers, Dr.med., Principal Investigator

Universitätsklinikum Leipzig AöR, Leipzig 04103, Germany; Recruiting
Dietger W. Niederwieser, Email: Dietger.Niederwieser@medizin.uni-leipzig.de
Dietger W. Niederwieser, Prof.Dr.med., Principal Investigator

Klinikum Lüdenscheid, Lüdenscheid 58515, Germany; Recruiting
Gerhard Heil, Prof.Dr.med., Email: gerhard.heil@klinikum-luedenscheid.de
Gerhard Heil, Prof.Dr.med., Principal Investigator

Philipps-Universität Marburg, Marburg 35032, Germany; Recruiting
Andreas Neubauer, Email: neubauer@staff.uni-marburg.de
Andreas Neubauer, Prof.Dr.med., Principal Investigator

TU München, München 86175, Germany; Recruiting
Katharina Götze, Prof.Dr.med., Email: k.goetze@lrz.tu-muenchen.de
Katharina Götze, PD Dr., Principal Investigator

University of Münster Medical Center, Münster 48149, Germany; Recruiting
Stefanie Wiebe, Dr.med., Email: stefanie.wiebe@ukmuenster.de
Kerstin Vehring, Email: kerstin.vehring@ukmuenster.de
Stefanie Wiebe, Dr.med., Principal Investigator

Ortenau Klinikum, Offenburg 77654, Germany; Recruiting
Irmgard Dresel
Irmgard Dresel, Dr. med., Principal Investigator

Studienzentrum Onkologie Ravensburg, Ravensburg 88212, Germany; Recruiting
Tobias Dechow, Dr.med., Email: dechow@onkonet.eu
Irina Gossen, Email: irina.gossen@onkonet.eu
Tobias Dechow, Dr.med., Principal Investigator

Eberhard Karls Universität Tübingen, Tübingen 72076, Germany; Recruiting
Helmut Salih, Prof.Dr.med., Email: helmut.salih@med.uni-tuebingen.de
Helmut Salih, Prof.Dr.med., Principal Investigator

Universitätsklinikum Ulm, Ulm 89081, Germany; Recruiting
Hartmut Döhner, Prof.Dr.med., Email: hartmut.doehner@uniklinik-ulm.de
Hartmut Döhner, Prof.Dr.med., Principal Investigator

Klinikum Villingen-Schwenningen, Villingen-Schwenningen 78050, Germany; Recruiting
Wolfram Brugger, Prof., Email: wolfram.brugger@sbk-vs.de
Wolfram Brugger, Prof.Dr.med., Principal Investigator

Additional Information

Starting date: August 2011
Last updated: August 27, 2014

Page last updated: August 23, 2015

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