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

NCT00146120 | Completed Phase 3

• 1 other identifier: AMLHD98A
• Study Type: interventional
• Target: 400
• Locations: 2 countries
• Sites: 22

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• relapse-free survival

  two years

Secondary Outcomes (1)

• overall survival

  two years

Interventions

Idarubicin DRUG

Cytosin-Arabinosid DRUG

Etoposide DRUG

All-trans Retinoid acid DRUG

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (22)

Department of Hematology / Oncology, University Hospital of Innsbruck

Innsbruck, 6020, Austria

Location

III Medical Department, Hematology and Oncology Center, Hanuschhospital Wien

Vienna, 1140, Austria

Location

Department of General Internal Medicine, University Hospital of Bonn

Bonn, 53127, Germany

Location

Department of Internal Medicine Hematology, Heinrich-Heine University

Düsseldorf, 40225, Germany

Location

Department of Interial Medicine III, City Hospital Frankfurt Am Main - Höchst

Frankfurt, 65927, Germany

Location

Medical Department IV, University of Gießen

Giessen, 35392, Germany

Location

Department of Interial Medicine, Wilhelm-Anton-Hospital Goch

Goch, 47574, Germany

Location

Centre of Interial Medicine, University of Göttingen

Göttingen, 37075, Germany

Location

Medical Department III of Hematology and Oncology, General Hospital Altona

Hamburg, 22763, Germany

Location

Department of Interial Medicine V, University of Heidelberg

Heidelberg, 69120, Germany

Location

Department of Interial Medicine I, University Hospital of Saarland

Homburg, 66421, Germany

Location

Medical Department II, City Hospital Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

Medical Department II, University Hospital of Kiel

Kiel, 24116, Germany

Location

Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach

Lebach, 66822, Germany

Location

I. Medical Department, City Hospital München-Schwabing

München, 80804, Germany

Location

Medical Department III, Clinical Center rechts der Isar

München, 81675, Germany

Location

Department of Hematology and Oncology, City Hospital Neunkirchen gGmbH

Neunkirchen, 66538, Germany

Location

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH

Oldenburg, 26133, Germany

Location

Department of Hematologie and Oncology, Caritas Hospital St. Theresa Saarbrücken

Saarbrücken, 66113, Germany

Location

Clinikal Cetner of Stuttgart, Center of Oncology

Stuttgart, 70174, Germany

Location

Medical Department I, Clinical Center of Stuttgart

Stuttgart, 70191, Germany

Location

Hospital of Barmherzige Brüder, I Medical Department

Trier, 54292, Germany

Location

Related Publications (6)

• Prochazka KT, Pregartner G, Rucker FG, Heitzer E, Pabst G, Wolfler A, Zebisch A, Berghold A, Dohner K, Sill H. Clinical implications of subclonal TP53 mutations in acute myeloid leukemia. Haematologica. 2019 Mar;104(3):516-523. doi: 10.3324/haematol.2018.205013. Epub 2018 Oct 11.

  PMID: 30309854 DERIVED

• Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O'Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Dohner K, Schlenk RF, Dohner H, Campbell PJ. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016 Jun 9;374(23):2209-2221. doi: 10.1056/NEJMoa1516192.

  PMID: 27276561 DERIVED

• Buchner T, Schlenk RF, Schaich M, Dohner K, Krahl R, Krauter J, Heil G, Krug U, Sauerland MC, Heinecke A, Spath D, Kramer M, Scholl S, Berdel WE, Hiddemann W, Hoelzer D, Hehlmann R, Hasford J, Hoffmann VS, Dohner H, Ehninger G, Ganser A, Niederwieser DW, Pfirrmann M. Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup. J Clin Oncol. 2012 Oct 10;30(29):3604-10. doi: 10.1200/JCO.2012.42.2907. Epub 2012 Sep 10.

  PMID: 22965967 DERIVED

• Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Rock J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, Spath D, Kundgen A, Schmidt-Wolf IG, Gotze K, Nachbaur D, Pfreundschuh M, Horst HA, Dohner H, Dohner K. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol. 2011 Apr 1;29(10):1364-72. doi: 10.1200/JCO.2010.30.7926. Epub 2011 Feb 22.

  PMID: 21343560 DERIVED

• Schlenk RF, Dohner K, Mack S, Stoppel M, Kiraly F, Gotze K, Hartmann F, Horst HA, Koller E, Petzer A, Grimminger W, Kobbe G, Glasmacher A, Salwender H, Kirchen H, Haase D, Kremers S, Matzdorff A, Benner A, Dohner H. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol. 2010 Oct 20;28(30):4642-8. doi: 10.1200/JCO.2010.28.6856. Epub 2010 Aug 30.

  PMID: 20805454 DERIVED

• Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, Wittke K, Du J, Groner S, Spath D, Krauter J, Ganser A, Dohner H, Fischer T, Dohner K; German-Austrian AML Study Group (AMLSG). Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood. 2009 Sep 17;114(12):2386-92. doi: 10.1182/blood-2009-03-209999. Epub 2009 Jul 14.

  PMID: 19602710 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Idarubicin; Etoposide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Hartmut Döhner, Prof. Dr.

  University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 5, 2005
• Study Start: May 1, 1998
• Primary Completion: May 1, 2005
• Study Completion: May 1, 2005
• Last Updated: February 9, 2009

Record last verified: 2008-12

Locations

DE (20); AU (2)