This is a randomized phase II, four-arm, open-label, multi-center study in adult patients with acute myeloid leukemia (AML) as defined in inclusion/exclusion criteria. The primary efficacy objective is to evaluate the impact of sequential or concurrent addition of 5-azacytidine to intensive induction chemotherapy with idarubicin and etoposide on the complete remission (CR) rate Sample size: 336 patients The treatment duration of an individual patient randomized into one of the three experimental arms (Arm B, C, D) (in case of application of induction, consolidation and maintenance therapy with Azacitidine) is about 30 months. The treatment duration for patients randomized into the standard arm of the study (Arm A) is about 7 months (in case of application of induction, consolidation and 2-yrs observation as maintenance (without treatment with Azacitidine)). In case of induction followed by consolidation with allogeneic Stem cell transplantation (SCT) the treatment duration per patient is about 6 months. Every patient will be followed until month 54 after inclusion into the study. Duration of the study for an individual patient including treatment (induction, consolidation \[chemotherapy or allogeneic SCT\], maintenance \[experimental arm with Azacitidine or observation\]) and follow-up period: 54 months
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
277
Induction therapy:100 mg/m2/day by continuous intravenous (IV) infusion on days 1-7 (total dose 700 mg/m2) Consolidation therapy: Younger adults (18 to 65 years): 3 g/m2/day by IV infusion over 3 hours every 12 hours on days 1, 2, and 3 (total dose 18 g/m2). Elderly patients (\>65 years): 1 g/m2/day by IV infusion over 3 hours every 12 hours on days 1, 2, and 3 (total dose 6 g/m2).
First induction therapy: Arm A, C, D: 12 mg/m2/day by IV push on days 1,3,5 (total dose 36 mg/m2). For elderly (\>65 yrs) patients only two doses of idarubicin are foreseen on days 1+3. Arm B: 12 mg/m2/day by IV push on days 6, 8 10 (total dose 36 mg/m2). For elderly (\>65 yrs) patients only two doses of idarubicin are foreseen on days 6+8. Second induction therapy: Arm A, C, D: 12 mg/m2/day by IV push on days 1 and 3 (total dose 24 mg/m2; for all age groups) Arm B: 12 mg/m2/day by IV push on days 6 and 8 (total dose 24 mg/m2; for all age groups).
Induction therapy: Arm A, C, D: 100 mg/m²/day by 1-hour IV infusion on days 1,2,3 (total dose 300 mg/m2). On days 1 and 3 start after idarubicin push. For elderly (\>65 yrs) patients only two doses of etoposide are foreseen on days 1+3. Arm B: 100 mg/m²/day by 1-hour IV infusion on days 6,7,8 (total dose 300 mg/m2). On days 6 and 8 start after idarubicin push. For elderly (\>65 yrs) patients only two doses of etoposide are foreseen on days 6+8.
Induction therapy: Arm B and C: 100 mg/m2/day by subcutaneous (SC) injection or 15-minute IV infusion on day 1 to day 5 (total dose 500 mg/m2). Azacitidine is always given prior to idarubicin and etoposide. Arm D: 100 mg/m2/day by SC injection or 15-minute IV infusion on days 4-8 (total dose 500 mg/m2). Azacitidine is always given prior to idarubicin and etoposide. Maintenance therapy: Arm B, C, D: 50 mg/m2/day by SC injection on days 1-5 (total dose 250 mg/m2) every 4 weeks. (Maintenance therapy is scheduled for a total duration of 2 years in patients with continuous CR)
Consolidation therapy: subcutaneously daily beginning on day 10 until neutrophil count \> 0.5 x 109/l.
Universitätsklinikum Innsbruck
Innsbruck, Austria
Krankenhaus der Barmherzigen Schwestern
Linz, Austria
Elisabethinen Krankenhaus Linz
Linz, Austria
Landeskliniken Salzburg
Salzburg, Austria
Hanuschkrankenhaus
Vienna, Austria
Universitätsklinikum Charité Berlin
Rates of complete remission (CR) after induction therapy
To evaluate the impact of sequential or concurrent addition of 5-azacytidine to intensive induction chemotherapy with idarubicin and etoposide on the CR rate
Time frame: 56 days
Event-free survival
Time frame: after two years of follow-up
Relapse-free survival
Time frame: after two years of follow-up
overall survival
Time frame: after two years of follow-up
days in hospital during each cycle and during the whole intervention
Time frame: 6 months
Rate of early deaths or hypoplastic deaths (ED/HD)
Time frame: 56 days
type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of non-hematological toxicity observed during different treatment cycles
Time frame: 6 months
quality of life assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30)
quality of life assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics according to Messerer et al \[35\].
Time frame: at the end of therapy (in average 6 months) and once a year in the follow-up
duration of leukopenia after each consolidation cycle
Time frame: 42 days
duration of neutropenia after each consolidation cycle
Time frame: 42 days
duration of thrombocytopenia after each consolidation cycle
Time frame: 42 days
duration of leukopenia after each induction cycle
Time frame: 28 days
duration of neutropenia after each induction cycle
Time frame: 28 days
duration of thrombocytopenia after each induction cycle
Time frame: 28 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Berlin, Germany
Knappschaftskrankenhaus Bochum-Langendreer
Bochum, Germany
Universitätsklinikum Bonn
Bonn, Germany
Städtisches Klinikum Braunschweig
Braunschweig, Germany
Klinikum Bremen-Mitte
Bremen, Germany
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