Clinical trial NCT01382147: Evaluation of "Dose-dense Therapy" by S-HAM in Comparison to Conventionally Timed Double Induction in Patients With Acute Myeloid Leukemia (AML)
Official title: A Randomized, Risk and Age Adapted Comparison of the Dose-Dense Regimen S-HAM (Sequential High Dose Cytosine Arabinoside and Mitoxantrone) Versus Standard Double Induction for Initial Chemotherapy of Adult Patients With Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: Kompetenznetz Leukämien
First posted: 2011-06-27
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluation weather early chemotherapy attempts for remission induction can improve the results of patients with Acute Myeloid Leukemia (AML), as compared to the standard group.


Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed AML (except acute promyelocytic leukemia) according to the WHO classification including patients with secondary AML and AML after preceding hematologic disorders
* Age 18 years or older
* Informed consent. Before any study specific procedure including randomisation is done or before study medication is administered, the subject, or legally acceptable representative, must have given written informed consent for participation in the study.

Exclusion Criteria:

* Acute promyelocytic leukemia (APL)
* Previous or concurrent malignancies other than AML
* Previous treatment with colony-stimulating factors, interleukins or interferons
* Known hypersensitivity to Escherichia coli derived products (e.g. Filgrastim, HUMULIN® Insulin, L-Asparaginase, HUMATROPE® Growth Hormone, INTRON A®)
* Antibody-based or cell-based immunotherapies
* Respiratory insufficiency with pO2 \<60 mmHg
* Heart failure NYHA III° or IV°
* Elevated creatinine \>2.0 mg/dl
* Elevated bilirubin \>2.0 mg/dl
* Pregnancy or lactation
* Females without adequate contraception
* Known HIV and/or hepatitis C infection
* Severe neurologic or psychiatric disease
* Psychiatric, addictive, or any disorder, which compromises ability to give truly informed consent for participation in this study
* Concerns for subject's compliance with the protocol procedures
* Lack of willingness to record and circulate personal disease-related informations defined in the study protocol

Primary outcomes:
measure: Overall response rate, aiming at a 15% increase in the CR/PR rate by S-HAM induction versus conventional double induction [TAD - HAM for younger patients, HAM (- HAM) for elderly patients].
timeFrame: 8 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bergisch-Gladbach
country: Germany
facility: Vinzenz-Pallotti-Hospital, Innere Abteilung
city: Berlin
country: Germany
facility: St. Hedwig Krankenhaus, Abteilung Innere Medizin
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukoelln, Innere Medizin - Haematologie und Onkologie
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch, Klinik für Haematologie, Onkologie und Tumorimmunologie
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau, Klinik fuer Innere Medizin, Haematologie, Onkologie, Gastroenterologie und Palliativmedizin
city: Berlin
country: Germany
facility: Evangelisches Waldkrankenhaus Spandau
city: Bielefeld
country: Germany
facility: Evangelisches Krankenhaus Bielefeld gGmbH, Klinik fuer Innere Medizin, Haematologie, Onkologie und Palliativmedizin
city: Bochum
country: Germany
facility: Augusta-Krankenanstalt, Klinik fuer Haematologie, Onkologie und Palliativmedizin
city: Bonn
country: Germany
facility: Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Innere Medizin I
city: Bottrop
country: Germany
facility: Knappschaftskrankenhaus Bottrop, Klinik fuer Innere Medizin
city: Dortmund
country: Germany
facility: St.-Johannes Hospital Dortmund, Klinik fuer Innere Medizin II
city: Eschweiler
country: Germany
facility: St.-Antonius-Hospital Eschweiler, Klinik fuer Haematologie und internistische Onkologie
city: Frankfurt / Oder
country: Germany
facility: Klinikum Frankfurt / Oder GmbH, Medizinische Klinik I
city: Gelsenkirchen
country: Germany
facility: St.-Josef-Hospital Gelsenkirchen-Horst, Klinik für Medizinische und Radiologische Onkologie, Hämatologie und Palliativmedizin
city: Gütersloh
country: Germany
facility: Städtisches Klinikum Gütersloh, Medizinische Klinik II
city: Hagen
country: Germany
facility: Kath. Krankenhaus Hagen GmbH, Klinik fuer Haematologie und Onkologie
city: Herford
country: Germany
facility: Klinikum Herford, Medizinische Klinik II
city: Köln
country: Germany
facility: Universitaetsklinikum Köln, Klinik I fuer Innere Medizin
city: Leverkusen
country: Germany
facility: Klinikum Leverkusen gGmbH, Medizinische Klinik III
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Medizinische Klinik A
city: Luebbeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Medizinische Klinik I, Haematologie / Onkologie
city: Mannheim
country: Germany
facility: Medizinische Fakultaet Mannheim der Universitaet Heidelberg, III. Medizinische Klinik Haematologie und Internistische Onkologie
city: Merseburg
country: Germany
facility: Carl-von-Basedow-Klinikum Saalekreis GmbH, Medizinische Klinik II
city: Moenchengladbach
country: Germany
facility: Krankenhaus Maria Hilf GmbH, Krankenhaus St. Franziskus, Medizinische Klinik I
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen Medizinische Klinik und Polikklinik III
city: Muenchen
country: Germany
facility: Staedtisches Klinikum Harlaching, Klinik für Onkologie und Haematologie
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück, Klinik fuer Haematologie / Onkologie
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef Paderborn, Klinik fuer Haematologie / Onkologie
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brüder , Klinik fuer internistische Onkologie und Haematologie
city: Siegen
country: Germany
facility: St.-Marien-Krankenhaus Siegen gem. GmbH, Medizinische Klinik III
city: Wiesbaden
country: Germany
facility: Stiftung Deutsche Klinik für Diagnostik GmbH, Zentrum fuer Knochenmark- und Stammzelltransplantation
city: Îdar-Oberstein
country: Germany
facility: Klinikum Idar-Oberstein GmbH, Innere Medizin I, Abteilung Haematologie / Onkologie
Study officials:
affiliation: Hospital of the University of Munich
name: Wolfgang Hiddemann, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kunadt D, Stasik S, Metzeler KH, Rollig C, Schliemann C, Greif PA, Spiekermann K, Rothenberg-Thurley M, Krug U, Braess J, Kramer A, Hochhaus A, Scholl S, Hilgendorf I, Brummendorf TH, Jost E, Steffen B, Bug G, Einsele H, Gorlich D, Sauerland C, Schafer-Eckart K, Krause SW, Hanel M, Hanoun M, Kaufmann M, Wormann B, Kramer M, Sockel K, Egger-Heidrich K, Herold T, Ehninger G, Burchert A, Platzbecker U, Berdel WE, Muller-Tidow C, Hiddemann W, Serve H, Stelljes M, Baldus CD, Neubauer A, Schetelig J, Thiede C, Bornhauser M, Middeke JM, Stolzel F; A. M. L. Cooperative Group (AMLCG), Study Alliance Leukemia (SAL). Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation. J Hematol Oncol. 2022 Sep 5;15(1):126. doi: 10.1186/s13045-022-01339-8.
citation: Konstandin NP, Pastore F, Herold T, Dufour A, Rothenberg-Thurley M, Hinrichsen T, Ksienzyk B, Tschuri S, Schneider S, Hoster E, Berdel WE, Woermann BJ, Sauerland MC, Braess J, Bohlander SK, Klein HG, Hiddemann W, Metzeler KH, Spiekermann K. Genetic heterogeneity of cytogenetically normal AML with mutations of CEBPA. Blood Adv. 2018 Oct 23;2(20):2724-2731. doi: 10.1182/bloodadvances.2018016840.
citation: Hubmann M, Kohnke T, Hoster E, Schneider S, Dufour A, Zellmeier E, Fiegl M, Braess J, Bohlander SK, Subklewe M, Sauerland MC, Berdel WE, Buchner T, Wormann B, Hiddemann W, Spiekermann K. Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse. Haematologica. 2014 Aug;99(8):1317-25. doi: 10.3324/haematol.2014.104133. Epub 2014 May 9.
citation: Greif PA, Dufour A, Konstandin NP, Ksienzyk B, Zellmeier E, Tizazu B, Sturm J, Benthaus T, Herold T, Yaghmaie M, Dorge P, Hopfner KP, Hauser A, Graf A, Krebs S, Blum H, Kakadia PM, Schneider S, Hoster E, Schneider F, Stanulla M, Braess J, Sauerland MC, Berdel WE, Buchner T, Woermann BJ, Hiddemann W, Spiekermann K, Bohlander SK. GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia. Blood. 2012 Jul 12;120(2):395-403. doi: 10.1182/blood-2012-01-403220. Epub 2012 May 30.