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

August 30, 2016 updated by: Michael Luebbert, University Hospital Freiburg

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
204

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Aachen, Germany, 52074
        • Klinikum der Technischen Universität Aachen
      • Berlin, Germany, 12351
        • Vivantes Klinikum Neukölln
      • Bochum, Germany, 44791
        • Augusta-Kranken-Anstalt gGmbH
      • Braunschweig, Germany, 38126
        • Klinikum Braunschweig
      • Bremen, Germany, 28239
        • DIAKO Ev. Diakonie-Krankenhaus gGmbH
      • Düsseldorf, Germany, 40225
        • Universitätsklinikum Düsseldorf
      • Düsseldorf, Germany, 40479
        • Marien Hospital Düsseldorf
      • Esslingen, Germany, 73730
        • Klinikum Esslingen GmbH
      • Frankfurt, Germany
        • Universität Frankfurt
      • Freiburg, Germany, 79106
        • Medizinische Universitätsklinik Freiburg
      • Hagen, Germany, 58095
        • St. Marien-Hospital Hagen
      • Halle, Germany, 06120
        • Universitätsklinikum Halle
      • Hamm, Germany, 59063
        • Evangelisches Krankenhaus Hamm gGmbH
      • Hannover, Germany, 30625
        • Med. Hochschule Hannover
      • Jena, Germany, 07747
        • Universitätsklinikum Jena
      • Lahr, Germany, 77933
        • Ortenau Klinikum Lahr-Ettenheim
      • Lebach, Germany, 66822
        • Caritas Krankenhaus Lebach
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig AöR
      • Lüdenscheid, Germany, 58515
        • Klinikum Lüdenscheid
      • Marburg, Germany, 35032
        • Philipps-Universität Marburg
      • München, Germany, 86175
        • TU München
      • Münster, Germany, 48149
        • University of Münster Medical Center
      • Offenburg, Germany, 77654
        • Ortenau Klinikum
      • Ravensburg, Germany, 88212
        • Studienzentrum Onkologie Ravensburg
      • Tübingen, Germany, 72076
        • Eberhard Karls Universität Tübingen
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm
      • Villingen-Schwenningen, Germany, 78050
        • Klinikum Villingen-Schwenningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Names:
  • Dacogen
Experimental: Decitabine+VPA
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
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Names:
  • Dacogen
Drug: VPA
VPA starting on day 6 of first cycle continuously throughout all treatment cycles
Other Names:
  • Valproic acid
Experimental: Decitabine+ATRA
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
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Names:
  • Dacogen
Drug: ATRA
ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
Other Names:
  • All-trans retinoic acid
Experimental: Decitabine+VPA+ATRA
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
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Names:
  • Dacogen
Drug: VPA
VPA starting on day 6 of first cycle continuously throughout all treatment cycles
Other Names:
  • Valproic acid
Drug: ATRA
ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
Other Names:
  • All-trans retinoic acid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Objective best response rate (complete remission (CR) and partial remission (PR))
Time Frame: 12 months after randomization of the last patient
12 months after randomization of the last patient

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Overall best response rate (CR, PR and antileukemic effect (ALE))
Time Frame: 12 months after randomization of the last patient
12 months after randomization of the last patient
progression-free survival (PFS)
Time Frame: 12 months after randomization of the last patient
12 months after randomization of the last patient
overall survival (OS)
Time Frame: 12 months after randomization of the last patient
12 months after randomization of the last patient
quality of life
Time Frame: until 4 weeks after study drug intake
until 4 weeks after study drug intake
safety and toxicity
Time Frame: until 4 weeks after study drug intake
until 4 weeks after study drug intake

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Freiburg

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Lübbert, MD, PhD, Department of Hematology/Oncology, University of Freiburg Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 23, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 24, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 31, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 00332/AMLSG14-09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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