Trial document




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  DRKS00000733

Trial Description

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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

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Trial Acronym

DECIDER Trial

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URL of the Trial

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Brief Summary in Lay Language

Trial objective of this trial is to investigate efficacy and safety of the histone deacetylase inhibitor Valproic acid and all-trans retinoic acid as additional therapy to Decitabine in older and unfit acute myeloid leukemia (AML) patients. Four treatment arms will be compared; Decitabine will be administered to all patients. 50 patients will be treated with Decitabine alone; 50 patients with Decitabine and Valproic acid (VPA); 50 patients will be administered Decitabine and Vesanoid (ATRA); 50 patients will receive Decitabine with VPA and ATRA. Furthermore data on tolerability and quality of life will be collected.

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Brief Summary in Scientific Language

Trial objectives is to investigate efficacy and safety of the histone deacetylase inhibitor Valproic acid (VPA) and all-trans retinoic acid (ATRA) as add-on to the epigenetically active drug Decitabine in older and unfit acute myeloid leukemia (AML) patients, with accompanying translational studies to identify molecular predictors of response.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00000733
  •   2011/04/19
  •   2009/03/23
  •   yes
  •   Approved
  •   76/10, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   2009-009916-33 
  •   NCT00867672  (ClinicalTrials.gov)
  •   4036719 
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Health Condition or Problem studied

  •   C92.9 -  Myeloid leukaemia, unspecified
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Interventions/Observational Groups

  •   i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
  •   i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks, and VPA (p.o.) from day 6 of first cycle continuously throughout all treatment cycles
  •   i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks and ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
  •   i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks and VPA (p.o.) from day 6 continuously throughout all treatment cycles and ATRA (45 mg/m² p.o.), from day 6 to day 28 of each treatment cycle
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Factorial
  •   II
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Primary Outcome

Objective best response rate (complete remission (CR) and partial remission (PR)) (at the end of the study)

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Secondary Outcome

Overall best response rate (CR, PR and antileukemic effect (ALE)), progression-free survival (PFS), overall survival (OS), quality of life (QOL), number of nights in hospital, safety (at the end of the study)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2011/12/27
  •   200
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   60   Years
  •   no maximum age
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Additional 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% BM blasts) 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. Age-adjusted normal cardiac and kidney function (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.

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Exclusion Criteria

1. AML of FAB subtype M3;
2. Previous remission-induction chemotherapy for MDS or AML, previous auto-/allografting;
3. Previous treatment with DAC, 5-azacytidine, VPA or another HDAC inhibitor, or ATRA;
4. "Low-dose" chemotherapy (e.g. hydroxyurea, cytosine arabinoside, melphalan, clofarabine etc.) within 8 weeks prior to DAC treatment, except for cytoreduction of leukocytosis ≥ 30 000/µl with hydroxyurea, as proscribed by the study protocol (section 7.3 and 7.4);
5. Treatment with tyrosine kinase Inhibitors, immunomodulating agents (IMIDS) and other investigational AML treatments within previous 8 weeks;
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));
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. Hepatitis B or C;
16. 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;
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.

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Addresses

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    • Universitätsklinikum Freiburg
    • Mr.  Prof. Dr. med.   Michael  Lübbert  
    • Hugstetter Strasse 49
    • 79095  Freiburg
    • Germany
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    • Universitätsklinikum Freiburg
    • Dr. med.  Bjoern  Hackanson 
    • Hugstetter Strasse 49
    • 79106  Freiburg
    • Germany
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    • Universitätsklinikum Freiburg
    • Mr.  Dr. med.  Bjoern  Hackanson 
    • Hugstetter Strasse 49
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2016/02/23
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Trial Publications, Results and other Documents

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