The disease under investigation is newly diagnosed Acute Myeloid Leucemia (AML) in elderly patients. MedDRA version: 13.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Vidaza (MA in USA and Switzerland)
Product Name: azacitidine
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: AZACITIDINE
CAS Number: 320672
Concentration unit
Sponsors
Universitaetsklinikum Muenster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with newly diagnosed AML (except APL) according to the FAB or WHO classification, including AML evolving from MDS or other hematological diseases and AML after previous cytotoxic therapy or radiation (secondary AML). • Bone marrow aspirate or biopsy must contain = 20% blasts of all nucleated cells or differential blood count must contain = 20% blasts. In AML FAB M6 = 30% of non-erythroid cells in the bone marrow must be leukemic blasts. In AML defined by cytogenetic aberrations the proportion of blasts may be =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients who are not eligible for standard chemotherapy as described in chapter 5.2 and 5.3 • Hyperleukocytosis (leukocytes > 20,000/µl) at study entry. These patients should be treated with hydroxyurea or receive leukocytapheresis treatment (leukocytes > 100 000/µl) according to routine practice and entered into the study when leukocyte counts of 20,000/µl and below are reached. This applies only for the controlled part of the study. • Patients with initial hyperleukocytosis above 20,000/µl can only be enrolled into the controlled part of the study, but not in the run-in dose finding part. • Known central nervous system manifestation of AML • Cardiac Disease: 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 (beta blockers or digoxin are permitted) • Chronically impaired renal function (creatinin clearance < 30 ml / min) • Inadequate liver function (ALT and AST = 2.5 x ULN) if not caused by leukemic infiltration • Total bilirubin = 1.5 x ULN if not caused by leukemic infiltration • Known HIV and/or hepatitis C infection • Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy • Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders • Uncontrolled active infection • Concurrent malignancies other than AML with an estimated life expectancy less than three years • History of organ allograft • Hypersensitivity to cytarabine (not including drug fever or exanthema), daunorubicin, azacytidine or mannitol • Previous treatment of AML except hydoxyurea and up to 2 days =100 mg/m2/d cytarabine • Previous therapy with 5-azacytidine (i.e. for an antecedent myelodysplastic syndrome) • Patients with investigational drug therapy outside of this trial during or within 4 weeks of study entry should be discussed with the study office wether a study participation is possible • Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparison of the median Event Free Survival (EFS) of all AML patients between the 5-azacytidine and the control group.;Secondary Objective: to compare •the median Event Free Survival (EFS) of AML patients with different cytogenetic and molecular risk groups1 •the median Overall Survival (OS) of all AML patients between the 5-azacytidine and the control group • the median Overall Survival (OS) of AML patients with different cytogenetic and molecular risk groups • the Relapse Free Survival (RFS) of AML patients between the 5-azacytidine and the control group •the rate of early response after the first induction cycle between the 5-azacytidine and the control group the CR rate of the 5-azacytidine with the control group • the CR rate of AML patients with different cytogenetic and molecular risk groups1 •the rate of molecular remissions of the 5-azacytidine with the control group •the toxicity of the 5-azacytidine and the control treatment ;Primary end point(s): The primary end point is the median Event Free Survival (EFS) of all AML patients. Event free survival (EFS): Time interval from day 1 of study treatment until treatment failure, relapse from CR, relapse from morphologic leukemia-free state, or death from any cause, whichever occurs first. The time point at which the patient is resistant to therapy or survives induction without a CR or Morphologic leukemia-free state will be noted. For a patient with none of these events before the end of study follow-up, observation of EFS will be censored at the date of his or her last follow-up examination. | — |
Countries
Germany
Outcome results
None listed