Acute Myeloid Leukemia
Conditions
Brief summary
This trial is a study on all-trans retinoic acid in combination with induction and consolidation therapy as well as pegfilgrastim after consolidation therapy in younger patients with newly diagnosed acute myeloid leukemia (AML).
Detailed description
First Induction Therapy: * Cytarabine 100 mg/m² cont. i.v. days 1-7 * Idarubicin 12 mg/m² i.v. days 1,3,5 * Etoposide 100 mg/m² i.v. days 1-3 * ± ATRA 45 mg/m² p.o. days 6-8 * ATRA 15 mg/m² p.o. days 9-21 Second Induction Therapy: * Cytarabine 100 mg/m² cont. i.v. days 1-7 * Idarubicin 12 mg/m² i.v. days 1 and 3 * Etoposide 100 mg/m² i.v. days 1-3 * ± ATRA 45 mg/m² p.o. days 6-8 * ATRA 15 mg/m² p.o. days 9-21 Consolidation Therapy: cohort 1 (\<= ID 336) * Cytarabine 3 g/m² 2x/die i.v. Tag 1,3,5 * ± ATRA 15 mg/m² p.o. Tag 6-21 * Pegfilgrastim 6 mg s.c day 10 cohort 2 (\> ID 336) * Cytarabine 3 g/m² 2x/die i.v. Tag 1,2,3 * ± ATRA 15 mg/m² p.o. Tag 4-21 * Pegfilgrastim 6 mg s.c day 8
Interventions
DRUGCytarabine
100mg/m² kont. i.v. day 1-7 (induction therapy) 3g/m² 2x/die i.v. day 1,3,5 or day 1,2,3
DRUGIdarubicin
12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle)
DRUGEtoposide
100mg/m² i.v. day 1-3 (induction therapy)
DRUGAll-trans retinoic acid
45mg/m² p.o. day 6-8 (induction therapy) 15mg/m² p.o. day 9-21 (induction therapy) 15mg/m² p.o. day 6-21 (consolidation therapy)
DRUGPegfilgrastim
6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)
Sponsors
University of Ulm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed AML defined according to the World Health Organization (WHO)-classification (excluding acute promyelocytic leukemia \[APL\]) * Ages 18-60 years * Written informed consent of each patient at study entry. * Molecular and cytogenetical diagnostics on initial bone marrow and peripheral blood specimen at the central reference laboratories
Exclusion criteria
* Bleeding independent of the AML * Acute promyelocytic leukemia * Uncontrollable infection * Participation in a concurrent clinical study * Insufficiency of the kidneys (creatinine \> 1.5x upper normal serum level), of the liver (bilirubin, AST or AP \> 2x upper normal serum level), severe obstructive or restrictive ventilation disorder, heart failure New York Heart Association (NYHA) III/IV * Severe neurological or psychiatric disorder interfering with ability to give an informed consent. * No consent for registration, storage and processing of the individual disease-characteristics and course. * Performance status WHO \> 2 * Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete remission (CR)-rate after induction therapy | after the second induction cycle |
| Relapse-free survival, one year after consolidation therapy with high-dose cytarabine considering different temporal sequences (1-3-5 versus 1-2-3) of the consolidation therapy | One year after consolidation therapy |
| Event-free survival | two years |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival | two years |
| Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle | during consolidation therapy |
| Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs | during therapy |
| Hematologic and non-hematologic toxicity after consolidation therapy with high-dose cytarabine considering the different consolidation schemes (day 1-3-5 versus day 1-2-3) | during consolidation therapy |
| Days in hospital after each consolidation cycle | after consolidation therapy |
| Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle | during consolidation therapy |
| Cumulative incidence of relapse | two years |
| Cumulative incidence of death | two years |
Countries
Austria, Germany
Outcome results
None listed