All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Description

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Brief Summary:

This is a study looking at all-trans retinoic acid in combination with standard induction and consolidation therapy in older patients with newly diagnosed acute myeloid leukemia (AML).

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Drug: Cytarabine; Drug: Idarubicin; Drug: All-trans retinoic acid; Drug: Mitoxantrone; Drug: Etoposid	Phase 3

Detailed Description:

First Induction Therapy:

• Cytarabine 100 mg/m² cont. i.v. days 1-5

• Idarubicin 12 mg/m² i.v. days 1, 3

  • ATRA 45 mg/m² p.o. days 4-6, ATRA 15 mg/m² p.o. days 7-28

Second Induction Therapy:

• Cytarabine 100 mg/m² cont. i.v. days 1-5

• Idarubicin 12 mg/m² i.v. days 1, 3

  • ATRA 45 mg/m² p.o. days 4-6, ATRA 15 mg/m² p.o. days 7-28

First Consolidation Therapy:

• Cytarabine 1000 mg/m² bid i.v. days 1-3

• Mitoxantrone 10 mg/m² i.v. days 2, 3

  • ATRA 15 mg/m² p.o. days 4-28

Second Consolidation Therapy

• Etoposide 100 mg/m² i.v. days 1-5

• Idarubicin 12 mg/m² i.v. days 1,3

  • ATRA 15 mg/m² p.o. days 4-28

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	500 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase III - Study on All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Study Start Date :	June 2004
Actual Primary Completion Date :	June 2009
Actual Study Completion Date :	January 2011

Arms and Interventions

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Intervention Details:

Drug: Cytarabine
100mg/m² kont. i.v. day 1-5 (induction therapy); 1000 mg/m² 2x/die i.v. day 1-3 (first consolidation cycle)
Drug: Idarubicin
12mg/m² i.v. day 1+3 (induction therapy); 12mg/m² i.v. Tag 1+3 (second consolidation cycle)
Drug: All-trans retinoic acid
45mg/m² p.o. day 4-6, 15mg/m² p.o. day 7-28 (induction therapy); 15mg/m² p.o. day 4-28 (consolidation therapy)
Drug: Mitoxantrone
10mg/m² i.v. day 2-3 (first consolidation cycle)
Drug: Etoposid
100mg/m² i.v. Tag 1-5 (second consolidation cycle)

Outcome Measures

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Primary Outcome Measures :

1. event-free survival [ Time Frame: two years ]

Secondary Outcome Measures :

1. kind, incidence, severity, temporal sequence and correlation of side effects of the study drugs [ Time Frame: during therapy ]
2. complete remission (CR) rate after induction therapy [ Time Frame: after second induction cycle ]
3. cumulative incidence of relapse [ Time Frame: two years ]
4. cumulative incidence of death [ Time Frame: two years ]
5. overall survival [ Time Frame: two years ]

Eligibility Criteria

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Ages Eligible for Study:	61 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Newly diagnosed AML defined according to the World Health Organization (WHO) classification (excluding acute promyelocytic leukemia [APL])
• Aged > 60 years
• All patients have to be informed about the character of the study. Written informed consent of each patient at study entry.
• Molecular and cytogenetical analyses on initial bone marrow and peripheral blood specimen have to be performed at the central reference laboratories.

Exclusion Criteria:

• Bleeding independent of the AML
• Acute promyelocytic leukemia
• Uncontrolled infection
• Participation in a concurrent clinical study
• Insufficiency of the kidneys (creatinine > 1.5 x upper normal serum level), of the liver (bilirubin, AST or AP > 2 x upper normal serum level), severe obstruction or restrictive ventilation disorder, heart failure New York Heart Association [NYHA] III/IV
• Severe neurological or psychiatric disorder interfering with ability of giving informed consent
• No consent for the registration, storage and processing of data concerning the characteristics of the AML and the individual course
• Performance status WHO > 2

Contacts and Locations

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Locations

Austria
Department of Hematology/Oncology, University Hospital of Innsbruck
Innsbruck, Austria, 6020
Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern
Linz, Austria, 4010
Medical Department III, St. Johann Hospital
Salzburg, Austria, 5020
Center of hematology and oncology, Hanusch Hospital
Wien, Austria, 1140
Germany
Department of Internal Medicine I, Central Hospital of Augsburg
Augsburg, Germany, 86856
Department of General Internal Medicine, University Hospital of Bonn
Bonn, Germany, 53127
Medical Department I, Hospital of Bremen-Mitte
Bremen, Germany, 28177
Department of Hematology and Oncology, Hospital Essen-Süd, Ev. Hospital of Essen-Werden
Essen, Germany, 45239
Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst
Frankfurt, Germany, 65929
Medical Department IV, University Hospital of Giessen
Giessen, Germany, 35392
Department of Internal Medicine, Wilhelm-Anton Hospital gGmbH
Goch, Germany, 47574
Centre of Internal Medicine, University Hospital of Göttingen
Göttingen, Germany, 37075
Department of Oncology and Hematology, University Hospital Eppendorf
Hamburg, Germany, 20246
Medical Department II, General Hospital Altona
Hamburg, Germany, 22763
Medical Department III, Hospital of Hanau
Hanau, Germany, 63450
Medical Department III, Hospital of Hannover-Siloah
Hannover, Germany, 30449
Department of Internal Medicine I, University Hospital of Saarland
Homburg, Germany, 66421
Medical Department II, City Hospital Karlsruhe gGmbH
Karlsruhe, Germany, 76133
Medical Department II, University Hospital of Kiel
Kiel, Germany, 24116
Department of Internal Medicine/Hematology and Oncology, Caritas Hospital Lebach
Lebach, Germany, 66822
Department of Hematology/Oncology, Clinical Center of Lüdenscheid
Lüdenscheid, Germany, 58515
Medical Department III, Clinical Center Rechts der Isar
München, Germany, 81675
Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH
Oldenburg, Germany, 26133
Department of Hematology and Oncology/Caritas Hospital St. Theresa
Saarbrücken, Germany, 66113
Department of Oncology, Clinical Center of Stuttgart
Stuttgart, Germany, 70174
Medical Department II, Diakonie Hospital
Stuttgart, Germany, 70176
I. Medical Department, Hospital of Barmerzigen Brüder
Trier, Germany, 54292
Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen
Villingen - Schwenningen, Germany, 78050
Medical Department I, Helios Hospital Wuppertal
Wuppertal, Germany, 42283

Sponsors and Collaborators

University of Ulm

Investigators

Principal Investigator:	Richard F Schlenk, Dr.	Department of Internal Medicine III, University of Ulm

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tassara M, Döhner K, Brossart P, Held G, Götze K, Horst HA, Ringhoffer M, Köhne CH, Kremers S, Raghavachar A, Wulf G, Kirchen H, Nachbaur D, Derigs HG, Wattad M, Koller E, Brugger W, Matzdorff A, Greil R, Heil G, Paschka P, Gaidzik VI, Göttlicher M, Döhner H, Schlenk RF. Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients. Blood. 2014 Jun 26;123(26):4027-36. doi: 10.1182/blood-2013-12-546283. Epub 2014 May 5. Erratum in: Blood. 2015 May 7;125(19):3037.

Schlenk RF, Taskesen E, van Norden Y, Krauter J, Ganser A, Bullinger L, Gaidzik VI, Paschka P, Corbacioglu A, Göhring G, Kündgen A, Held G, Götze K, Vellenga E, Kuball J, Schanz U, Passweg J, Pabst T, Maertens J, Ossenkoppele GJ, Delwel R, Döhner H, Cornelissen JJ, Döhner K, Löwenberg B. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. 2013 Aug 29;122(9):1576-82. doi: 10.1182/blood-2013-05-503847. Epub 2013 Jul 17.

Responsible Party:	Prof. Dr. Richard Schlenk, PD Dr., University of Ulm
ClinicalTrials.gov Identifier:	NCT00151255 History of Changes
Other Study ID Numbers:	AMLSG06-04
First Posted:	September 8, 2005
Last Update Posted:	April 19, 2017
Last Verified:	April 2017

Keywords provided by Prof. Dr. Richard Schlenk, University of Ulm:

age > 60 years

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Cytarabine; Mitoxantrone; Idarubicin; Tretinoin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents	Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antibiotics, Antineoplastic; Keratolytic Agents; Dermatologic Agents