Study of Decitabine Alone or in Combination With Valproic Acid and All-trans Retinoic Acid in Acute Myeloid Leukemia
DECIDER
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
1 other identifier
interventional
204
1 country
27
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2011
Typical duration for phase_2
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 23, 2009
CompletedFirst Posted
Study publicly available on registry
March 24, 2009
CompletedStudy Start
First participant enrolled
August 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2016
CompletedAugust 31, 2016
August 1, 2016
3.5 years
March 23, 2009
August 30, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective best response rate (complete remission (CR) and partial remission (PR))
12 months after randomization of the last patient
Secondary Outcomes (5)
Overall best response rate (CR, PR and antileukemic effect (ALE))
12 months after randomization of the last patient
progression-free survival (PFS)
12 months after randomization of the last patient
overall survival (OS)
12 months after randomization of the last patient
quality of life
until 4 weeks after study drug intake
safety and toxicity
until 4 weeks after study drug intake
Study Arms (4)
Decitabine
EXPERIMENTALi.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Decitabine+VPA
EXPERIMENTALi.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
Decitabine+ATRA
EXPERIMENTALi.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
Decitabine+VPA+ATRA
EXPERIMENTALi.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
Interventions
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
VPA starting on day 6 of first cycle continuously throughout all treatment cycles
ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
Eligibility Criteria
You may qualify if:
- Written informed consent obtained according to international guidelines and local law;
- Male or female patients aged \> 60 years without upper age limit;
- 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;
- Patients with \< 30 000 leukocytes/μl;
- Performance status ECOG 0, 1, 2;
- Creatinine \< 2.0 mg/dl (unless leukemia-related);
- Ability to understand the nature of the study and the study related procedures and to comply with them.
You may not qualify if:
- AML of FAB subtype M3;
- Previous remission-induction chemotherapy for MDS or AML, previous allografting;
- Previous treatment with DAC, 5-azacytidine, VPA or another HDAC inhibitor, or ATRA;
- "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;
- 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;
- Treatment with cytokines within previous 4 weeks;
- Concomitant therapy which is considered relevant for the evaluation of efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy);
- Cardiac insufficiency NYHA IV;
- Insufficient hepatic function (bilirubin, AST or ALT \> = 2.5 x Upper Limit of Normal (ULN)) (unless leukemia-related);
- Fatal hepatic function disorder during treatment with valproic acid in siblings;
- Hepatic porphyria;
- Manifest serious pancreatic function disorder;
- Plasmatic coagulation disorder not related to AML;
- Known active hepatitis B or C;
- Known HIV infection;
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (27)
Klinikum der Technischen Universität Aachen
Aachen, 52074, Germany
Vivantes Klinikum Neukölln
Berlin, 12351, Germany
Augusta-Kranken-Anstalt gGmbH
Bochum, 44791, Germany
Klinikum Braunschweig
Braunschweig, 38126, Germany
DIAKO Ev. Diakonie-Krankenhaus gGmbH
Bremen, 28239, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, 40225, Germany
Marien Hospital Düsseldorf
Düsseldorf, 40479, Germany
Klinikum Esslingen GmbH
Esslingen am Neckar, 73730, Germany
Universität Frankfurt
Frankfurt, Germany
Medizinische Universitätsklinik Freiburg
Freiburg im Breisgau, 79106, Germany
St. Marien-Hospital Hagen
Hagen, 58095, Germany
Universitätsklinikum Halle
Halle, 06120, Germany
Evangelisches Krankenhaus Hamm gGmbH
Hamm, 59063, Germany
Med. Hochschule Hannover
Hanover, 30625, Germany
Universitätsklinikum Jena
Jena, 07747, Germany
Ortenau Klinikum Lahr-Ettenheim
Lahr, 77933, Germany
Caritas Krankenhaus Lebach
Lebach, 66822, Germany
Universitätsklinikum Leipzig AöR
Leipzig, 04103, Germany
Klinikum Lüdenscheid
Lüdenscheid, 58515, Germany
Philipps-Universität Marburg
Marburg, 35032, Germany
TU München
München, 86175, Germany
University of Münster Medical Center
Münster, 48149, Germany
Ortenau Klinikum
Offenburg, 77654, Germany
Studienzentrum Onkologie Ravensburg
Ravensburg, 88212, Germany
Eberhard Karls Universität Tübingen
Tübingen, 72076, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Klinikum Villingen-Schwenningen
Villingen-Schwenningen, 78050, Germany
Related Publications (5)
Bresser H, Schmoor C, Grishina O, Pfeifer D, Thomas J, Rehman UU, Crysandt M, Jost E, Thol F, Heuser M, Gotze KS, Schlenk RF, Salih HR, Schittenhelm MM, Heil G, Schwaenen C, Muller-Tidow C, Brugger W, Kundgen A, de Wit M, Giagounidis A, Scholl S, Neubauer A, Krauter J, Bug G, May AM, Wasch R, Duyster J, Dohner K, Ganser A, Dohner H, Hackanson B, Becker H, Lubbert M. Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine. Eur J Haematol. 2025 Feb;114(2):231-237. doi: 10.1111/ejh.14304. Epub 2024 Oct 13.
PMID: 39400388DERIVEDThomas J, Rehman UU, Bresser H, Grishina O, Pfeifer D, Sollier E, Dohner K, Plass C, Becker H, Schmoor C, de Wit M, Lubbert M. Continued decitabine/all-trans retinoic acid treatment: extended complete remission in an elderly AML patient with multi-hit TP53 lesions and complex-monosomal karyotype. Clin Epigenetics. 2024 Sep 11;16(1):126. doi: 10.1186/s13148-024-01737-4.
PMID: 39261919DERIVEDJavorniczky NR, Grishina O, Hund I, Pantic M, Pfeifer D, Schmoor C, Thomas J, Duyster J, Becker H, Lubbert M. Long-term decitabine/retinoic acid maintenance treatment in an elderly sAML patient with high-risk genetics. Clin Epigenetics. 2023 Nov 28;15(1):185. doi: 10.1186/s13148-023-01596-5.
PMID: 38012682DERIVEDLubbert M, Grishina O, Schmoor C, Schlenk RF, Jost E, Crysandt M, Heuser M, Thol F, Salih HR, Schittenhelm MM, Germing U, Kuendgen A, Gotze KS, Lindemann HW, Muller-Tidow C, Heil G, Scholl S, Bug G, Schwaenen C, Giagounidis A, Neubauer A, Krauter J, Brugger W, De Wit M, Wasch R, Becker H, May AM, Duyster J, Dohner K, Ganser A, Hackanson B, Dohner H; DECIDER Study Team. Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 x 2, Phase II Trial. J Clin Oncol. 2020 Jan 20;38(3):257-270. doi: 10.1200/JCO.19.01053. Epub 2019 Dec 3.
PMID: 31794324DERIVEDGrishina O, Schmoor C, Dohner K, Hackanson B, Lubrich B, May AM, Cieslik C, Muller MJ, Lubbert M. DECIDER: 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. BMC Cancer. 2015 May 26;15:430. doi: 10.1186/s12885-015-1432-5.
PMID: 26008690DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Lübbert, MD, PhD
Department of Hematology/Oncology, University of Freiburg Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
March 23, 2009
First Posted
March 24, 2009
Study Start
August 1, 2011
Primary Completion
February 1, 2015
Study Completion
February 1, 2016
Last Updated
August 31, 2016
Record last verified: 2016-08