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

• ClinicalTrials.gov Identifier: NCT00151255
• Recruitment Status: Completed
• First Posted: September 8, 2005
• Last Update Posted: April 19, 2017
• Sponsor: University of Ulm
• Information provided by (Responsible Party): Prof. Dr. Richard Schlenk, University of Ulm

Study Description

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

• 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

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

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

• Ages Eligible for Study: 61 Years and older (Adult, Older Adult)
• 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

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

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