Clinical trial NCT00151255: All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: age > 60 years
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2005-09-08
Enrollment: 500
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Eligibility 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

Primary outcomes:
measure: event-free survival
timeFrame: two years
Secondary outcomes:
measure: kind, incidence, severity, temporal sequence and correlation of side effects of the study drugs
timeFrame: during therapy
measure: complete remission (CR) rate after induction therapy
timeFrame: after second induction cycle
measure: cumulative incidence of relapse
timeFrame: two years
measure: cumulative incidence of death
timeFrame: two years
measure: overall survival
timeFrame: two years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Department of Hematology/Oncology, University Hospital of Innsbruck
city: Linz
country: Austria
facility: Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern
city: Salzburg
country: Austria
facility: Medical Department III, St. Johann Hospital
city: Wien
country: Austria
facility: Center of hematology and oncology, Hanusch Hospital
city: Augsburg
country: Germany
facility: Department of Internal Medicine I, Central Hospital of Augsburg
city: Bonn
country: Germany
facility: Department of General Internal Medicine, University Hospital of Bonn
city: Bremen
country: Germany
facility: Medical Department I, Hospital of Bremen-Mitte
city: Essen
country: Germany
facility: Department of Hematology and Oncology, Hospital Essen-Süd, Ev. Hospital of Essen-Werden
city: Frankfurt
country: Germany
facility: Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst
city: Giessen
country: Germany
facility: Medical Department IV, University Hospital of Giessen
city: Goch
country: Germany
facility: Department of Internal Medicine, Wilhelm-Anton Hospital gGmbH
city: Göttingen
country: Germany
facility: Centre of Internal Medicine, University Hospital of Göttingen
city: Hamburg
country: Germany
facility: Department of Oncology and Hematology, University Hospital Eppendorf
city: Hamburg
country: Germany
facility: Medical Department II, General Hospital Altona
city: Hanau
country: Germany
facility: Medical Department III, Hospital of Hanau
city: Hannover
country: Germany
facility: Medical Department III, Hospital of Hannover-Siloah
city: Homburg
country: Germany
facility: Department of Internal Medicine I, University Hospital of Saarland
city: Karlsruhe
country: Germany
facility: Medical Department II, City Hospital Karlsruhe gGmbH
city: Kiel
country: Germany
facility: Medical Department II, University Hospital of Kiel
city: Lebach
country: Germany
facility: Department of Internal Medicine/Hematology and Oncology, Caritas Hospital Lebach
city: Lüdenscheid
country: Germany
facility: Department of Hematology/Oncology, Clinical Center of Lüdenscheid
city: München
country: Germany
facility: Medical Department III, Clinical Center Rechts der Isar
city: Oldenburg
country: Germany
facility: Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH
city: Saarbrücken
country: Germany
facility: Department of Hematology and Oncology/Caritas Hospital St. Theresa
city: Stuttgart
country: Germany
facility: Department of Oncology, Clinical Center of Stuttgart
city: Stuttgart
country: Germany
facility: Medical Department II, Diakonie Hospital
city: Trier
country: Germany
facility: I. Medical Department, Hospital of Barmerzigen Brüder
city: Villingen - Schwenningen
country: Germany
facility: Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen
city: Wuppertal
country: Germany
facility: Medical Department I, Helios Hospital Wuppertal
Study officials:
affiliation: University of Ulm
name: Richard F Schlenk, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tassara M, Dohner K, Brossart P, Held G, Gotze K, Horst HA, Ringhoffer M, Kohne 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, Gottlicher M, Dohner 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.
citation: Schlenk RF, Taskesen E, van Norden Y, Krauter J, Ganser A, Bullinger L, Gaidzik VI, Paschka P, Corbacioglu A, Gohring G, Kundgen A, Held G, Gotze K, Vellenga E, Kuball J, Schanz U, Passweg J, Pabst T, Maertens J, Ossenkoppele GJ, Delwel R, Dohner H, Cornelissen JJ, Dohner K, Lowenberg 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.