Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result

Study Overview
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Brief Summary
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The concept of the investigators risk-adapted multicenter treatment trial for younger adults, AML HD98A, is based on the results of the AML HD93 trial and on published data. Definition of risk groups is different compared to the AML HD93 trial; high-risk: refractory disease after first induction therapy and/or high risk karyotype [abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p), complex]; intermediate-risk: complete remission after induction therapy and intermediate risk karyotype [normal, abn(11q23), abn(16q22), other rare aberrations]; low-risk: complete remission after induction therapy and low risk karyotype [t(8;21)]. Patients exhibiting a t(15;17) were treated in a separated trial (APL HD95). Treatment consists of a first induction therapy with ICE followed by a second cycle ICE in case of response to first induction therapy. Patients with refractory disease after first induction therapy are assigned to a salvage therapy with A-HAM (all-trans retinoic acid, high-dose cytarabine and mitoxantrone) and the search for potential hematopoietic stem cell donors is extended from the family to unrelated persons. All patients achieving a CR after induction therapy with ICE are assigned to a first consolidation therapy with HAM. For intermediate-risk patients a peripheral stem cell or a bone marrow harvest are intended during the hematological recovery after the first consolidation. Second consolidation therapy was stratified according to the risk definition. For high risk patients a allogeneic transplantation is assigned from a related or unrelated donor preferentially after a dose-intensified conditioning therapy. All patients with intermediate risk and an HLA-matched family donor are assigned to allogeneic transplantation. Intermediate-risk patients without a family donor and normal karyotype at diagnosis are randomized between an autologous stem cell transplantation and a second course of HAM. The other intermediate-risk patients are assigned to autologous transplantation. For low-risk patients a second course of HAM is assigned.

Official Title
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Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Idarubicin
* Drug: Cytosin-Arabinosid
* Drug: Etoposide
* Drug: All-trans Retinoid acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with AML, de Novo or secondary after Myelodysplasy, or with therapy-induced AML after healed primary malignom; or refractory anemia with excess of blasts in transformation (RAEB-t); the diagnosis must be confirmed morphological, cytochemical and with immunological phenotyping Cytogenetical tests must be performed for each patient Age: 16 - 60 years All patients have to be informed about the character of the study. Written informed consent of each patient at study entry. Exclusion Criteria: Organic insufficiency: Insufficiency of the kidneys (Crea > 1.5 x upper normal serum level), or insufficiency of the liver (bilirubin, SGOT or AP > 2 x upper normal serum level) uncaused by the AML; severe obstruction or restrictive ventilation disorder, heart failure with a ejection fraction < 0.5 Secondary malignom Other severe diseases Pregnancy Participation in an concurrent clinical study

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Idarubicin|nan|
|Drug: Cytosin-Arabinosid|nan|
|Drug: Etoposide|nan|
|Drug: All-trans Retinoid acid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse-free survival |  | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | two years |