Evaluation of "Dose-dense Therapy" by S-HAM in Comparison to Conventionally Timed Double Induction in Patients With Acute Myeloid Leukemia (AML) (AMLCG 2008)
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Ara-C, Mitoxantrone, Daunorubicin, Thioguanin
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
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
Sites / Locations
- Vinzenz-Pallotti-Hospital, Innere Abteilung
- St. Hedwig Krankenhaus, Abteilung Innere Medizin
- Vivantes Klinikum Neukoelln, Innere Medizin - Haematologie und Onkologie
- HELIOS Klinikum Berlin-Buch, Klinik für Haematologie, Onkologie und Tumorimmunologie
- Vivantes Klinikum Spandau, Klinik fuer Innere Medizin, Haematologie, Onkologie, Gastroenterologie und Palliativmedizin
- Evangelisches Waldkrankenhaus Spandau
- Evangelisches Krankenhaus Bielefeld gGmbH, Klinik fuer Innere Medizin, Haematologie, Onkologie und Palliativmedizin
- Augusta-Krankenanstalt, Klinik fuer Haematologie, Onkologie und Palliativmedizin
- Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Innere Medizin I
- Knappschaftskrankenhaus Bottrop, Klinik fuer Innere Medizin
- St.-Johannes Hospital Dortmund, Klinik fuer Innere Medizin II
- St.-Antonius-Hospital Eschweiler, Klinik fuer Haematologie und internistische Onkologie
- Klinikum Frankfurt / Oder GmbH, Medizinische Klinik I
- St.-Josef-Hospital Gelsenkirchen-Horst, Klinik für Medizinische und Radiologische Onkologie, Hämatologie und Palliativmedizin
- Städtisches Klinikum Gütersloh, Medizinische Klinik II
- Kath. Krankenhaus Hagen GmbH, Klinik fuer Haematologie und Onkologie
- Klinikum Herford, Medizinische Klinik II
- Universitaetsklinikum Köln, Klinik I fuer Innere Medizin
- Klinikum Leverkusen gGmbH, Medizinische Klinik III
- Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Medizinische Klinik A
- Universitätsklinikum Schleswig-Holstein, Medizinische Klinik I, Haematologie / Onkologie
- Medizinische Fakultaet Mannheim der Universitaet Heidelberg, III. Medizinische Klinik Haematologie und Internistische Onkologie
- Carl-von-Basedow-Klinikum Saalekreis GmbH, Medizinische Klinik II
- Krankenhaus Maria Hilf GmbH, Krankenhaus St. Franziskus, Medizinische Klinik I
- Klinikum der Universitaet Muenchen Medizinische Klinik und Polikklinik III
- Staedtisches Klinikum Harlaching, Klinik für Onkologie und Haematologie
- Klinikum Osnabrück, Klinik fuer Haematologie / Onkologie
- Brüderkrankenhaus St. Josef Paderborn, Klinik fuer Haematologie / Onkologie
- Krankenhaus Barmherzige Brüder , Klinik fuer internistische Onkologie und Haematologie
- St.-Marien-Krankenhaus Siegen gem. GmbH, Medizinische Klinik III
- Stiftung Deutsche Klinik für Diagnostik GmbH, Zentrum fuer Knochenmark- und Stammzelltransplantation
- Klinikum Idar-Oberstein GmbH, Innere Medizin I, Abteilung Haematologie / Onkologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
S-HAM
TAD-HAM (younger) or HAM-HAM (elderly)
Arm Description
S-HAM (S-HAMescalated for younger patients and S-HAMbasis for elderly patients)
is TAD-9 - HAM for younger patients (with 2 mandatory induction cycles) and HAM (- HAM) for the elderly patients with the second HAM cycle only applied in the case of inadequate blast clearance (> 5%) in the day 16 bone marrow aspirate
Outcomes
Primary Outcome Measures
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].
Secondary Outcome Measures
Full Information
NCT ID
NCT01382147
First Posted
June 23, 2011
Last Updated
December 4, 2017
Sponsor
Prof. Dr. Wolfgang Hiddemann
Collaborators
Kompetenznetz Leukämien
1. Study Identification
Unique Protocol Identification Number
NCT01382147
Brief Title
Evaluation of "Dose-dense Therapy" by S-HAM in Comparison to Conventionally Timed Double Induction in Patients With Acute Myeloid Leukemia (AML)
Acronym
AMLCG 2008
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
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
July 1, 2009 (Actual)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
July 5, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Dr. Wolfgang Hiddemann
Collaborators
Kompetenznetz Leukämien
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
396 (Actual)
8. Arms, Groups, and Interventions
Arm Title
S-HAM
Arm Type
Experimental
Arm Description
S-HAM (S-HAMescalated for younger patients and S-HAMbasis for elderly patients)
Arm Title
TAD-HAM (younger) or HAM-HAM (elderly)
Arm Type
Active Comparator
Arm Description
is TAD-9 - HAM for younger patients (with 2 mandatory induction cycles) and HAM (- HAM) for the elderly patients with the second HAM cycle only applied in the case of inadequate blast clearance (> 5%) in the day 16 bone marrow aspirate
Intervention Type
Drug
Intervention Name(s)
Ara-C, Mitoxantrone, Daunorubicin, Thioguanin
Intervention Description
Chemotherapy
Primary Outcome Measure Information:
Title
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].
Time Frame
8 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang Hiddemann, Prof. Dr.
Organizational Affiliation
Hospital of the University of Munich
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vinzenz-Pallotti-Hospital, Innere Abteilung
City
Bergisch-Gladbach
ZIP/Postal Code
51429
Country
Germany
Facility Name
St. Hedwig Krankenhaus, Abteilung Innere Medizin
City
Berlin
ZIP/Postal Code
10115
Country
Germany
Facility Name
Vivantes Klinikum Neukoelln, Innere Medizin - Haematologie und Onkologie
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Facility Name
HELIOS Klinikum Berlin-Buch, Klinik für Haematologie, Onkologie und Tumorimmunologie
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Vivantes Klinikum Spandau, Klinik fuer Innere Medizin, Haematologie, Onkologie, Gastroenterologie und Palliativmedizin
City
Berlin
ZIP/Postal Code
13585
Country
Germany
Facility Name
Evangelisches Waldkrankenhaus Spandau
City
Berlin
ZIP/Postal Code
13589
Country
Germany
Facility Name
Evangelisches Krankenhaus Bielefeld gGmbH, Klinik fuer Innere Medizin, Haematologie, Onkologie und Palliativmedizin
City
Bielefeld
ZIP/Postal Code
44791
Country
Germany
Facility Name
Augusta-Krankenanstalt, Klinik fuer Haematologie, Onkologie und Palliativmedizin
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Innere Medizin I
City
Bonn
ZIP/Postal Code
53113
Country
Germany
Facility Name
Knappschaftskrankenhaus Bottrop, Klinik fuer Innere Medizin
City
Bottrop
ZIP/Postal Code
46242
Country
Germany
Facility Name
St.-Johannes Hospital Dortmund, Klinik fuer Innere Medizin II
City
Dortmund
ZIP/Postal Code
44137
Country
Germany
Facility Name
St.-Antonius-Hospital Eschweiler, Klinik fuer Haematologie und internistische Onkologie
City
Eschweiler
ZIP/Postal Code
52249
Country
Germany
Facility Name
Klinikum Frankfurt / Oder GmbH, Medizinische Klinik I
City
Frankfurt / Oder
ZIP/Postal Code
15236
Country
Germany
Facility Name
St.-Josef-Hospital Gelsenkirchen-Horst, Klinik für Medizinische und Radiologische Onkologie, Hämatologie und Palliativmedizin
City
Gelsenkirchen
ZIP/Postal Code
45899
Country
Germany
Facility Name
Städtisches Klinikum Gütersloh, Medizinische Klinik II
City
Gütersloh
ZIP/Postal Code
33332
Country
Germany
Facility Name
Kath. Krankenhaus Hagen GmbH, Klinik fuer Haematologie und Onkologie
City
Hagen
ZIP/Postal Code
58095
Country
Germany
Facility Name
Klinikum Herford, Medizinische Klinik II
City
Herford
ZIP/Postal Code
32049
Country
Germany
Facility Name
Universitaetsklinikum Köln, Klinik I fuer Innere Medizin
City
Köln
ZIP/Postal Code
50924
Country
Germany
Facility Name
Klinikum Leverkusen gGmbH, Medizinische Klinik III
City
Leverkusen
ZIP/Postal Code
51375
Country
Germany
Facility Name
Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Medizinische Klinik A
City
Ludwigshafen
ZIP/Postal Code
67063
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein, Medizinische Klinik I, Haematologie / Onkologie
City
Luebbeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
Medizinische Fakultaet Mannheim der Universitaet Heidelberg, III. Medizinische Klinik Haematologie und Internistische Onkologie
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Carl-von-Basedow-Klinikum Saalekreis GmbH, Medizinische Klinik II
City
Merseburg
ZIP/Postal Code
06217
Country
Germany
Facility Name
Krankenhaus Maria Hilf GmbH, Krankenhaus St. Franziskus, Medizinische Klinik I
City
Moenchengladbach
ZIP/Postal Code
41063
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen Medizinische Klinik und Polikklinik III
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Staedtisches Klinikum Harlaching, Klinik für Onkologie und Haematologie
City
Muenchen
ZIP/Postal Code
81545
Country
Germany
Facility Name
Klinikum Osnabrück, Klinik fuer Haematologie / Onkologie
City
Osnabrück
ZIP/Postal Code
49076
Country
Germany
Facility Name
Brüderkrankenhaus St. Josef Paderborn, Klinik fuer Haematologie / Onkologie
City
Paderborn
ZIP/Postal Code
33098
Country
Germany
Facility Name
Krankenhaus Barmherzige Brüder , Klinik fuer internistische Onkologie und Haematologie
City
Regensburg
ZIP/Postal Code
93049
Country
Germany
Facility Name
St.-Marien-Krankenhaus Siegen gem. GmbH, Medizinische Klinik III
City
Siegen
ZIP/Postal Code
57072
Country
Germany
Facility Name
Stiftung Deutsche Klinik für Diagnostik GmbH, Zentrum fuer Knochenmark- und Stammzelltransplantation
City
Wiesbaden
ZIP/Postal Code
65191
Country
Germany
Facility Name
Klinikum Idar-Oberstein GmbH, Innere Medizin I, Abteilung Haematologie / Onkologie
City
Îdar-Oberstein
ZIP/Postal Code
55743
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
36064577
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.
Results Reference
derived
PubMed Identifier
30337300
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.
Results Reference
derived
PubMed Identifier
24816240
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.
Results Reference
derived
PubMed Identifier
22649106
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.
Results Reference
derived
Learn more about this trial
Evaluation of "Dose-dense Therapy" by S-HAM in Comparison to Conventionally Timed Double Induction in Patients With Acute Myeloid Leukemia (AML)
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