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Leukemia, Myelocytic, AcutePhase 3DaunoDoubleNCT02140242

Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML

A Phase 3 study testing study part 1 - dose daunorubicin and induction cycles in people with Leukemia, Myelocytic, Acute, run by Technische Universität Dresden at 38 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The proposed trial will address two clinically important questions for younger patients with newly diagnosed acute myeloid leukemia (AML): the optimal dose of daunorubicin in induction therapy and the necessity of a second induction cycle in patients with a good response after the first induction. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Leukemia, Myelocytic, Acute
What is being tested?
study part 1 - dose daunorubicin and induction cycles
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
721 participants
Where
38 sitesin 2 countries
Study dates
16 Apr 2014to 25 Apr 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Newly diagnosed AML other than acute promyelocytic leukemia (APL) according to WHO criteria, i.e. bone marrow aspirate or biopsy must contain ≥20% blasts of all nucleated cells or differential blood count must contain ≥20% blasts. In acute erythroid leukemia, ≥20% blasts in all non-erythroid bone marrow cells. In AML defined by cytogenetic aberrations, the rate of blasts may be <20%. Secondary AMLs are eligible for inclusion.
  • Age 18- inkl.65 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Adequate liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
  • Total bilirubin ≤ 1.5 times the upper limit of normal
  • alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times upper limit of normal
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  • Creatinine ≤ 1.5 times upper limit of normalExclusion Criteria:
  • Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 50% as assessed by transthoracic two-dimensional echocardiography ("M Mode") or multiple gated acquisition scan (MUGA scan)
  • Signed informed consent
  • Women must fulfill at least one of the following criteria in order to be eligible for trial inclusion:
  • Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum follicle stimulating hormone (FSH) > 40 U/ml)
  • Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy
  • Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device - IUD).
  • Sexual abstinence
  • Vasectomy of the sexual partner

Who cannot join

  • Patients who are not eligible for standard chemotherapy as assessed by the treating physician
  • Central nervous system manifestation of AML
  • Cardiac disease: i.e. heart failure New York Heart Association (NYHA) III or IV; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Patients undergoing renal dialysis
  • Chronic pulmonary disease with clinical relevant hypoxia
  • Known HIV or Hepatitis infection
Show all 16Show fewer
  • Uncontrolled active infection
  • Medical conditions other than AML with an estimated life expectancy below 6 months
  • Previous treatment of AML except hydroxyurea up to 5 days
  • Relapsed or primary refractory AML
  • Acute promyelocytic leukemia
  • Previous anthracycline-containing chemotherapy
  • Treatment with any known non-marketed drug substance or experimental therapy within 4 weeks prior to enrollment
  • Incapability of understanding purpose and possible consequences of the trial
  • Pregnant or breastfeeding women
  • Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)

Trial locations and contacts

38 sites in 2 countries.

38 sites in 2 countries

Germany33 sites

  • Uniklinik RWTH Aachen

    Aachen, 52074

  • Klinikum Altenburger Land GmbH

    Altenburg

  • Klinikum Augsburg

    Augsburg

  • Sozialstiftung Bamberg Klinikum am Bruderwald

    Bamberg

  • Charite Campus Benjamin Franklin

    Berlin

  • Helios Klinikum Berlin-Buch

    Berlin

  • Klinikum Bielefeld

    Bielefeld

  • Augusta Kliniken Bochum Hattingen

    Bochum, 44791

  • Ev. Diakonie-Krankenhaus gGmbH Bremen

    Bremen

  • Klinikum Chemnitz GmbH

    Chemnitz

  • Carl.Thiem-Klinikum Cottbus gGmbH

    Cottbus

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden

  • Krankenhaus Düren gem. GmbH

    Düren

  • Marienhospital Düsseldorf GmbH

    Düsseldorf

  • Universitätsklinikum Erlangen

    Erlangen

  • Universitätsklinikum Essen

    Essen

  • Johann Wolfgang Goethe-Universität Frankfurt am Main

    Frankfurt am Main

  • Universitätsklinikum Halle (Saale)

    Halle

  • Asklepios Klinik St. Georg

    Hamburg

  • St. Marien-Hospital Hamm

    Hamm

  • Universitätsklinikum Heidelberg

    Heidelberg

  • St. Bernward Krankenhaus Hildesheim

    Hildesheim

  • Universitätsklinikum Jena

    Jena, 07740

  • Westpfalz-Klinikum GmbH

    Kaiserslautern

  • Städtisches Krankenhaus Kiel

    Kiel

  • Gemeinschaftsklinikum Mittelrhein GmbH

    Koblenz

  • Universitätsklinikum Leipzig

    Leipzig

  • Universitätsklinikum Gießen und Marburg

    Marburg

  • Universitätsklinikum Münster

    Münster

  • Klinikum Nürnberg-Nord

    Nuremberg

  • Diakonie-Klinikum Schwäbisch Hall gGmbH

    Schwäbisch Hall

  • Robert-Bosch-Krankenhaus

    Stuttgart

  • Rems-Murr-Klinikum Winnenden

    Winnenden

Other trials in Germany

Czechia5 sites

  • Interní klinika LF Masarykovy univerzity a Fakultní nemocnice Brno

    Brno

  • Faculty Hospital Hradec Králové, II. Clinic of international medicine

    Hradec Králové

  • Fakultní nemocnice Olomouc

    Olomouc

  • Fakultní nemocnice Královské Vinohrady

    Prague

  • Ústav hematologie a krevní transfuze (ÚHKT)

    Prague

Other trials in Czechia

About this study

Official title: Randomized Comparison Between Two Dose Levels of Daunorubicin and Between One Versus Two Cycles of Induction Therapy for Adult Patients With Acute Myeloid Leukemia ≤65 Years

The proposed trial will address two clinically important questions for younger patients with newly diagnosed acute myeloid leukemia (AML): the optimal dose of daunorubicin in induction therapy and the necessity of a second induction cycle in patients with a good response after the first induction. The primary endpoint is the rate of good responders. Secondary outcomes will be relapse-free survival, overall survival and minimal residual disease kinetics. Patients will be recruited in about 40 treatment centers of the Study Alliance Leukemia study group over a period of 40 months. The results will be of great clinical relevance: First, the study could facilitate the establishment or confirmation of the optimal daunorubicin dose.

Read the detailed description

In the first part of the trial, patients will be randomly assigned to receive either 90 mg/m2 or 60 mg/m2 daunorubicin in the first induction cycle in addition to standard dosed cytarabine. Assuming a superiority of 90 mg/m2, 436 patients will be recruited. In the second part of the trial, good responders will be randomized to receive either a second or no further induction cycle. Assuming a non-inferiority of the single induction regarding the rate of complete remissions, a number of 360 patients will be included in the second part. Furthermore, in case of a non-inferiority of single versus double induction in good responders, about half of all younger AML patients could be spared a second induction cycle, leading to a reduction in treatment-related mortality, fewer days spent in hospital and improved quality of life.

As a result of the preplanned interim analysis of part I, the sponsor decided to suspend randomization in trial part I and to offer all patients the standard dose of 60 mg/m2 daunorubicin in both induction cycles (part I and II of the trial). Because of this an Amendment was sent to and approved by regulatories and ethics comitee.

The inclusion age was raised to 65 years based on the current German treatment guidelines in which patients up to the age of 65 are considered eligible for intensive induction chemotherapy with DA60 [Onkopedia-Leitlinie 2017].

Being tested
study part 1 - dose daunorubicin, induction cycles
Keywords
AML, leukemia, induction treatment, daunorubicin, 7+3
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • study part 1 - dose daunorubicinDrug

    standard induction dose of daunorubicin 60 mg/m2 on days 3-5

  • induction cyclesProcedure or surgery

    single induction cycle versus double induction cycles (only patients with good response after first induction) Allocation is randomized for cytogenetic risk.

Study groups in NCT02140242
Study groupRoleWhat they receive
daunorubicin 60 mg/m2Active comparatorstudy part 1 - dose daunorubicin standard dose daunorubicin in induction 1 (60 mg/m2) on days 3-5
Receives: Drug: study part 1 - dose daunorubicin
Double inductionActive comparatorstudy part 2: induction cycles double induction (only patients with good response)
Receives: Procedure: induction cycles
Single inductionExperimentalstudy part 2: induction cycles single induction (only patients with good response)
Receives: Procedure: induction cycles

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. response rate after first induction

    To investigate whether a higher dose of daunorubicin in induction chemotherapy leads to an increase in hematological good responders defined as having <5% myeloid blasts on day 15 after start of induction therapy.

    Measured: day 15

  2. Rate complete remissions

    To investigate whether the rate of complete remissions (CR) after single induction is similar to that after double induction in patients with good response to induction I.

    Measured: day 35 after final induction

Secondary outcomes (11)

  1. rate cytogenetic and molecular complete remissions

    To investigate whether a higher dose of daunorubicin in induction chemotherapy will lead to an increase in cytogenetic and molecular complete remissions.

    Measured: day 35

  2. event-free survival (EFS)

    To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.

    Measured: 5 years

  3. relapse-free survival (RFS)

    To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.

    Measured: 5 years

  4. overall survival (OS)

    To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.

    Measured: 5 years

  5. Correlation between Minimal Residual Disease (MRD) and EFS, RFS, OS

    To correlate the level of cytogenetic and molecular minimal residual disease after induction treatment with survival outcomes EFS, RFS and OS.

    Measured: day 35

  6. Rate of induction deaths

    Rate of induction deaths (until day 60 or beginning of consolidation treatment - whichever occurs first)

    Measured: day 60

  7. Incidence of serious infectious complications

    Incidence of serious infectious complications Grades 3-4 (Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0

    Measured: day 35

  8. Sonographic cardiac left ventricular ejection fraction

    Sonographic cardiac left ventricular ejection fraction

    Measured: day 35

  9. Serum levels of pro-brain natriuretic peptide (por-BNP) and Troponin-T

    Serum levels of pro-BNP and Trop-T

    Measured: day 35

  10. Incidence of CTCAE grade ≥3 cardiac complications

    Incidence of CTCAE grade ≥3 cardiac complications

    Measured: day 35

  11. Rate of early deaths

    Rate of early deaths (2 weeks)

    Measured: week 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2014 (estimated)
  2. Study start16 Apr 2014
  3. Primary completion25 Apr 2022
  4. Study completion25 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
721 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02140242
Sponsor's protocol ID
TUD-2DAUNO-058
Acronym
DaunoDouble
Status last verified
Sep 2023
First submitted
9 May 2014
Last updated
15 Sep 2023
Results posted
No
Data monitoring committee
No

Publications

  • Dendorfer SM, Schmidt-Brucken K, Kramer M, Steffen B, Schliemann C, Mikesch JH, Alakel N, Herbst R, Hanel M, Hanoun M, Kaufmann M, Weinbergerova B, Schafer-Eckart K, Sauer T, Neubauer A, Burchert A, Baldus CD, Mertova J, Jost E, Niemann D, Novak J, Krause SW, Scholl S, Hochhaus A, Held G, Szotkowski T, Rank A, Schmid C, Fransecky L, Kayser S, Schaich M, Fiebig F, Haake A, Schetelig J, Middeke JM, Stolzel F, Platzbecker U, Thiede C, Muller-Tidow C, Berdel WE, Ehninger G, Mayer J, Serve H, Bornhauser M, Rollig C. Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in AML Induction Therapy. Am J Hematol. 2026 Mar;101(3):512-520. doi: 10.1002/ajh.70160. Epub 2026 Jan 5.

    PubMed 41492073

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing study part 1 - dose daunorubicin and induction cycles in people with Leukemia, Myelocytic, Acute, run by Technische Universität Dresden at 38 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Germany, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

response rate after first induction (time frame: day 15). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02140242, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023.

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