Clinical trial NCT00146120: Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
Official title: Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2005-09-05
Enrollment: 400
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: relapse-free survival
timeFrame: two years
Secondary outcomes:
measure: overall survival
timeFrame: two years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Department of Hematology / Oncology, University Hospital of Innsbruck
city: Wien
country: Austria
facility: III Medical Department, Hematology and Oncology Center, Hanuschhospital Wien
city: Bonn
country: Germany
facility: Department of General Internal Medicine, University Hospital of Bonn
city: Düsseldorf
country: Germany
facility: Department of Internal Medicine Hematology, Heinrich-Heine University
city: Frankfurt
country: Germany
facility: Department of Interial Medicine III, City Hospital Frankfurt Am Main - Höchst
city: Gießen
country: Germany
facility: Medical Department IV, University of Gießen
city: Goch
country: Germany
facility: Department of Interial Medicine, Wilhelm-Anton-Hospital Goch
city: Göttingen
country: Germany
facility: Centre of Interial Medicine, University of Göttingen
city: Hamburg
country: Germany
facility: Medical Department III of Hematology and Oncology, General Hospital Altona
city: Heidelberg
country: Germany
facility: Department of Interial Medicine V, University of Heidelberg
city: Homburg
country: Germany
facility: Department of Interial Medicine I, University Hospital of Saarland
city: Karlsruhe
country: Germany
facility: Medical Department II, City Hospital Karlsruhe gGmbH
city: Kiel
country: Germany
facility: Medical Department II, University Hospital of Kiel
city: Lebach
country: Germany
facility: Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach
city: München
country: Germany
facility: I. Medical Department, City Hospital München-Schwabing
city: München
country: Germany
facility: Medical Department III, Clinical Center rechts der Isar
city: Neunkirchen
country: Germany
facility: Department of Hematology and Oncology, City Hospital Neunkirchen gGmbH
city: Oldenburg
country: Germany
facility: Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH
city: Saarbrücken
country: Germany
facility: Department of Hematologie and Oncology, Caritas Hospital St. Theresa Saarbrücken
city: Stuttgart
country: Germany
facility: Clinikal Cetner of Stuttgart, Center of Oncology
city: Stuttgart
country: Germany
facility: Medical Department I, Clinical Center of Stuttgart
city: Trier
country: Germany
facility: Hospital of Barmherzige Brüder, I Medical Department
Study officials:
affiliation: University of Ulm
name: Hartmut Döhner, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
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