The concept of our 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.

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Idarubicin  Drug: Cytosin-Arabinosid  Drug: Etoposide  Drug: All-trans Retinoid acid	Phase III

Further Study Details: 

Primary Outcomes: relapse-free survival
Secondary Outcomes: overall survival
Expected Total Enrollment:  400

Ages Eligible for Study:  16 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

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

Austria
      Department of Hematology / Oncology, University Hospital of Innsbruck, Innsbruck,  6020,  Austria
      III Medical Department, Hematology and Oncology Center, Hanuschhospital Wien, Wien,  1140,  Austria
Germany
      Department of General Internal Medicine, University Hospital of Bonn, Bonn,  53127,  Germany
      Department of Internal Medicine Hematology, Heinrich-Heine University, Düsseldorf,  40225,  Germany
      Department of Interial Medicine III, City Hospital Frankfurt Am Main - Höchst, Frankfurt,  65927,  Germany
      Medical Department IV, University of Gießen, Giessen,  35392,  Germany
      Department of Interial Medicine, Wilhelm-Anton-Hospital Goch, Goch,  47574,  Germany
      Centre of Interial Medicine, University of Göttingen, Göttingen,  37075,  Germany
      Medical Department III of Hematology and Oncology, General Hospital Altona, Hamburg,  22763,  Germany
      Department of Interial Medicine V, University of Heidelberg, Heidelberg,  69120,  Germany
      Department of Interial Medicine I, University Hospital of Saarland, Homburg,  66421,  Germany
      Medical Department II, City Hospital Karlsruhe gGmbH, Karlsruhe,  76133,  Germany
      Medical Department II, University Hospital of Kiel, Kiel,  24116,  Germany
      Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach, Lebach,  66822,  Germany
      Medical Department III, Clinical Center rechts der Isar, München,  81675,  Germany
      I. Medical Department, City Hospital München-Schwabing, München,  80804,  Germany
      Department of Hematology and Oncology, City Hospital Neunkirchen gGmbH, Neunkirchen,  66538,  Germany
      Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH, Oldenburg,  26133,  Germany
      Department of Hematologie and Oncology, Caritas Hospital St. Theresa Saarbrücken, Saarbrücken,  66113,  Germany
      Medical Department I, Clinical Center of Stuttgart, Stuttgart,  70191,  Germany
      Clinikal Cetner of Stuttgart, Center of Oncology, Stuttgart,  70174,  Germany
      Hospital of Barmherzige Brüder, I Medical Department, Trier,  54292,  Germany

Study chairs or principal investigators

Hartmut Döhner, Prof. Dr.,  Principal Investigator,  Department of Internal Medicine III, University of Ulm   

Study ID Numbers:  AMLHD98A
Last Updated:  September 2, 2005
Record first received:  September 1, 2005
ClinicalTrials.gov Identifier:  NCT00146120
Health Authority: Germany: Federal Institute for Drugs and Medicinal Devices
ClinicalTrials.gov processed this record on 2005-09-13