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. Patients at the age of 18 to 65 years. MedDRA version: 21.0 Level: LL
Conditions
Interventions
Product Name: Daunoblastin
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Daunorubicin
Other descriptive name: DAUNORUBICIN HYDROCHLORIDE
Concentration unit: mg m
Sponsors
Technische Universität Dresden
Eligibility
Sex/Gender
All
Inclusion 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 40 U/ml) o Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy o Continuous and correct application of a contraception method with a Pearl Index of =65 years) yes F.1.3.1 Number of subjects for this age range 568
Exclusion criteria
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 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 anthracyclin-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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Trial part I: To investigate whether a higher dose of daunorubicin in induction chemotherapy leads to an in-crease in good responders defined as having <5% myeloid blasts on day 15 after start of induction - Trial part II: To investigate whether the rate of CR/CRi after single induction is similar to that after double induction in patients with a good response to induction I. ;Secondary Objective: - To investigate whether a higher dose of daunorubicin in induction chemotherapy will lead to an increase in cytogenetic and molecular complete remissions. - 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 is similar after single versus double induction in patients with good response to induction I. - To investigate a possible correlation between the level of cytogenetic and molecular minimal residual disease after induction treatment with survival outcomes EFS, RFS and OS.;Primary end point(s): - Trial part I: Rate (percentage) of good responders two weeks after start of induction defined by the presence of <5% myeloid blasts on day 15 after start of IT. - Trial part II: Rate (percentage) of complete hematological remissions (CR; CRi) as defined by standard criteria [Döhner 2010] after induction treatment.;Timepoint(s) of evaluation of this end point: - Trial part I: 15 days after start of induction I - Trial part II: day 35 after start of last in-study induction | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy Endpoints: o Rate of complete molecular and cytogenetic remissions o Event-free survival o Relapse-free survival o Overall survival - Safety Endpoints: o Rate of early deaths (2 weeks) and induction deaths (until day 60 or beginning of consolidation treatment – whichever occurs first) o Incidence of serious infectious complications (Grades 3-4 CTCAE V4.0) o Incidence of CTCAE grade =3 cardiac complications;Timepoint(s) of evaluation of this end point: - Efficacy Endpoints: day 35 after start of last in-study induction; 2 years - Safety Endpoints: regulary; within 2 weeks after start of induction; until day 60 or beginning of consolidation treatment – whichever occurs first | — |
Countries
Czech Republic, Germany
Contacts
Public ContactMK I Bereich Klinische Studien
Medizinische Fakultät der TU Dresden
Outcome results
None listed