- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02140242
Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML (DaunoDouble)
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
Study Overview
Status
Conditions
Intervention / Treatment
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].
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Annett Haake
- Phone Number: +049 - 0351 458 3965
- Email: annett.haake@ukdd.de
Study Contact Backup
- Name: Frank Fiebig
- Phone Number: +049 - 0351 458 5198
- Email: frank.fiebig@ukdd.de
Study Locations
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Brno, Czechia
- Interní klinika LF Masarykovy univerzity a Fakultní nemocnice Brno
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Hradec Králové, Czechia
- Faculty Hospital Hradec Králové, II. Clinic of international medicine
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Olomouc, Czechia
- Fakultni Nemocnice Olomouc
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Praha, Czechia
- Fakultni nemocnice Kralovske Vinohrady
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Praha, Czechia
- Ústav hematologie a krevní transfuze (ÚHKT)
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Aachen, Germany, 52074
- Uniklinik RWTH Aachen
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Altenburg, Germany
- Klinikum Altenburger Land GmbH
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Augsburg, Germany
- Klinikum Augsburg
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Bamberg, Germany
- Sozialstiftung Bamberg Klinikum am Bruderwald
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Berlin, Germany
- Charite Campus Benjamin Franklin
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Berlin, Germany
- Helios Klinikum Berlin-Buch
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Bielefeld, Germany
- Klinikum Bielefeld
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Bochum, Germany, 44791
- Augusta Kliniken Bochum Hattingen
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Bremen, Germany
- Ev. Diakonie-Krankenhaus gGmbH Bremen
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Chemnitz, Germany
- Klinikum Chemnitz GmbH
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Cottbus, Germany
- Carl.Thiem-Klinikum Cottbus gGmbH
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Dresden, Germany
- Universitatsklinikum Carl Gustav Carus Dresden
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Düren, Germany
- Krankenhaus Düren gem. GmbH
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Düsseldorf, Germany
- Marienhospital Düsseldorf GmbH
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Erlangen, Germany
- Universitatsklinikum Erlangen
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Essen, Germany
- Universitatsklinikum Essen
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Frankfurt am Main, Germany
- Johann Wolfgang Goethe-Universität Frankfurt am Main
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Halle, Germany
- Universitatsklinikum Halle (Saale)
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Hamburg, Germany
- Asklepios Klinik St. Georg
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Hamm, Germany
- St. Marien-Hospital Hamm
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Heidelberg, Germany
- UniversitatsKlinikum Heidelberg
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Hildesheim, Germany
- St. Bernward Krankenhaus Hildesheim
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Jena, Germany, 07740
- Universitätsklinikum Jena
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Kaiserslautern, Germany
- Westpfalz-Klinikum GmbH
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Kiel, Germany
- Städtisches Krankenhaus Kiel
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Koblenz, Germany
- Gemeinschaftsklinikum Mittelrhein GmbH
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Leipzig, Germany
- Universitätsklinikum Leipzig
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Marburg, Germany
- Universitätsklinikum Giessen und Marburg
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Münster, Germany
- Universitatsklinikum Munster
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Nürnberg, Germany
- Klinikum Nürnberg-Nord
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Schwäbisch Hall, Germany
- Diakonie-Klinikum Schwäbisch Hall gGmbH
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Stuttgart, Germany
- Robert-Bosch-Krankenhaus
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Winnenden, Germany
- Rems-Murr-Klinikum Winnenden
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- 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
Exclusion criteria:
- 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
- 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: daunorubicin 60 mg/m2
study part 1 - dose daunorubicin standard dose daunorubicin in induction 1 (60 mg/m2) on days 3-5
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standard induction dose of daunorubicin 60 mg/m2 on days 3-5
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Active Comparator: Double induction
study part 2: induction cycles double induction (only patients with good response)
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single induction cycle versus double induction cycles (only patients with good response after first induction) Allocation is randomized for cytogenetic risk.
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Experimental: Single induction
study part 2: induction cycles single induction (only patients with good response)
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single induction cycle versus double induction cycles (only patients with good response after first induction) Allocation is randomized for cytogenetic risk.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
response rate after first induction
Time Frame: day 15
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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.
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day 15
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Rate complete remissions
Time Frame: day 35 after final induction
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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.
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day 35 after final induction
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
rate cytogenetic and molecular complete remissions
Time Frame: day 35
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To investigate whether a higher dose of daunorubicin in induction chemotherapy will lead to an increase in cytogenetic and molecular complete remissions.
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day 35
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event-free survival (EFS)
Time Frame: 5 years
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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.
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5 years
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relapse-free survival (RFS)
Time Frame: 5 years
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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.
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5 years
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overall survival (OS)
Time Frame: 5 years
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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.
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5 years
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Correlation between Minimal Residual Disease (MRD) and EFS, RFS, OS
Time Frame: day 35
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To correlate the level of cytogenetic and molecular minimal residual disease after induction treatment with survival outcomes EFS, RFS and OS.
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day 35
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Rate of induction deaths
Time Frame: day 60
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Rate of induction deaths (until day 60 or beginning of consolidation treatment - whichever occurs first)
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day 60
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Incidence of serious infectious complications
Time Frame: day 35
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Incidence of serious infectious complications Grades 3-4 (Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0
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day 35
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Sonographic cardiac left ventricular ejection fraction
Time Frame: day 35
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Sonographic cardiac left ventricular ejection fraction
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day 35
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Serum levels of pro-brain natriuretic peptide (por-BNP) and Troponin-T
Time Frame: day 35
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Serum levels of pro-BNP and Trop-T
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day 35
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Incidence of CTCAE grade ≥3 cardiac complications
Time Frame: day 35
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Incidence of CTCAE grade ≥3 cardiac complications
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day 35
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Rate of early deaths
Time Frame: week 2
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Rate of early deaths (2 weeks)
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week 2
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Christoph Röllig, Prof. Dr., Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TUD-2DAUNO-058
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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