Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML (DaunoDouble)
Leukemia, Myelocytic, Acute
About this trial
This is an interventional treatment trial for Leukemia, Myelocytic, Acute focused on measuring AML, leukemia, induction treatment, daunorubicin, 7+3
Eligibility Criteria
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)
Sites / Locations
- Interní klinika LF Masarykovy univerzity a Fakultní nemocnice Brno
- Faculty Hospital Hradec Králové, II. Clinic of international medicine
- Fakultní nemocnice Olomouc
- Fakultní nemocnice Královské Vinohrady
- Ústav hematologie a krevní transfuze (ÚHKT)
- Uniklinik RWTH Aachen
- Klinikum Altenburger Land GmbH
- Klinikum Augsburg
- Sozialstiftung Bamberg Klinikum am Bruderwald
- Charite Campus Benjamin Franklin
- Helios Klinikum Berlin-Buch
- Klinikum Bielefeld
- Augusta Kliniken Bochum Hattingen
- Ev. Diakonie-Krankenhaus gGmbH Bremen
- Klinikum Chemnitz GmbH
- Carl.Thiem-Klinikum Cottbus gGmbH
- Universitätsklinikum Carl Gustav Carus Dresden
- Krankenhaus Düren gem. GmbH
- Marienhospital Düsseldorf GmbH
- Universitätsklinikum Erlangen
- Universitätsklinikum Essen
- Johann Wolfgang Goethe-Universität Frankfurt am Main
- Universitätsklinikum Halle (Saale)
- Asklepios Klinik St. Georg
- St. Marien-Hospital Hamm
- Universitätsklinikum Heidelberg
- St. Bernward Krankenhaus Hildesheim
- Universitätsklinikum Jena
- Westpfalz-Klinikum GmbH
- Städtisches Krankenhaus Kiel
- Gemeinschaftsklinikum Mittelrhein GmbH
- Universitätsklinikum Leipzig
- Universitätsklinikum Gießen und Marburg
- Universitätsklinikum Münster
- Klinikum Nürnberg-Nord
- Diakonie-Klinikum Schwäbisch Hall gGmbH
- Robert-Bosch-Krankenhaus
- Rems-Murr-Klinikum Winnenden
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Active Comparator
Experimental
daunorubicin 60 mg/m2
Double induction
Single induction
study part 1 - dose daunorubicin standard dose daunorubicin in induction 1 (60 mg/m2) on days 3-5
study part 2: induction cycles double induction (only patients with good response)
study part 2: induction cycles single induction (only patients with good response)