Study on All-Trans Retinoic Acid, Induction and Consolidation Therapy, and Pegfilgrastim After Consolidation Therapy in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT00151242 | Completed Phase 2

• 1 other identifier: AMLSG07-04
• Study Type: interventional
• Target: 920
• Locations: 2 countries
• Sites: 34

Brief Summary

This trial is a study on all-trans retinoic acid in combination with induction and consolidation therapy as well as pegfilgrastim after consolidation therapy in younger patients with newly diagnosed acute myeloid leukemia (AML).

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Complete remission (CR)-rate after induction therapy

  after the second induction cycle

• Relapse-free survival, one year after consolidation therapy with high-dose cytarabine considering different temporal sequences (1-3-5 versus 1-2-3) of the consolidation therapy

  One year after consolidation therapy

• Event-free survival

  two years

Secondary Outcomes (8)

• Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs

  during therapy

• Cumulative incidence of relapse

  two years

• Cumulative incidence of death

  two years

• Overall survival

  two years

• Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle

  during consolidation therapy

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: Cytarabine; Drug: Idarubicin; Drug: Etoposide; Drug: Pegfilgrastim

2

EXPERIMENTAL

Drug: Cytarabine; Drug: Idarubicin; Drug: Etoposide; Drug: All-trans retinoic acid; Drug: Pegfilgrastim

Interventions

Cytarabine DRUG

100mg/m² kont. i.v. day 1-7 (induction therapy) 3g/m² 2x/die i.v. day 1,3,5 or day 1,2,3

1; 2

Idarubicin DRUG

12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle)

1; 2

Etoposide DRUG

100mg/m² i.v. day 1-3 (induction therapy)

1; 2

All-trans retinoic acid DRUG

45mg/m² p.o. day 6-8 (induction therapy) 15mg/m² p.o. day 9-21 (induction therapy) 15mg/m² p.o. day 6-21 (consolidation therapy)

2

Pegfilgrastim DRUG

6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)

Also known as: Neulasta

1; 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Newly diagnosed AML defined according to the World Health Organization (WHO)-classification (excluding acute promyelocytic leukemia \[APL\])
• Ages 18-60 years
• Written informed consent of each patient at study entry.
• Molecular and cytogenetical diagnostics on initial bone marrow and peripheral blood specimen at the central reference laboratories

You may not qualify if:

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

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (34)

Department of Hematology/Oncology, University Hospital Innsbruck

Innsbruck, 6020, Austria

Location

Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern

Linz, 4010, Austria

Location

Medical Department III, St. Johann-Hospital

Salzburg, 5020, Austria

Location

Center of Hematology and Oncology, Hanusch-Hospital

Vienna, 1140, Austria

Location

Department of General Internal Medicine, University Hospital of Bonn

Bonn, 53127, Germany

Location

Medical Department I, Hospital Bremen-Mitte

Bremen, 28177, Germany

Location

Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf

Düsseldorf, 40225, Germany

Location

Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden

Essen, 45239, Germany

Location

Medical Department III, Hematology/Oncology, University of Frankfurt

Frankfurt, 60590, Germany

Location

Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst

Frankfurt, 65929, Germany

Location

Internal Medicine I, University of Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Medical Department IV, University Hospital of Giessen

Giessen, 35392, Germany

Location

Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH

Goch, 47574, Germany

Location

Centre of Internal Medicine, University Hospital Göttingen

Göttingen, 37075, Germany

Location

Department of Oncology and Hematology, University Hospital Eppendorf

Hamburg, 20246, Germany

Location

Medical Department II, Hematology and Oncology, General Hospital Altona

Hamburg, 22763, Germany

Location

Medical Department III, Clinical Center Hanau

Hanau, 63450, Germany

Location

Medical Department III, Hospital Hannover-Siloah

Hanover, 30449, Germany

Location

Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Department of Internal Medicine I, University Hospital of Saarland

Homburg, 66421, Germany

Location

Medical Department II, City Hospital Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

Medical Department II, University Hospital of Kiel

Kiel, 24116, Germany

Location

Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach

Lebach, 66822, Germany

Location

Department of Hematology and Oncology, Hospital of Lüdenscheid

Lüdenscheid, 58505, Germany

Location

Department of Hematology and Internal Oncology, University Hospital of Mainz

Mainz, 55101, Germany

Location

Medical Department III, Clinical Center Rechts der Isar

München, 81675, Germany

Location

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH

Oldenburg, 26133, Germany

Location

Department of Hematology and Oncology, Caritas Hospital St. Theresia

Saarbrücken, 66113, Germany

Location

Department of Oncology, Clinical Center of Stuttgart

Stuttgart, 70174, Germany

Location

Medical Department II, Diakonie Hospital

Stuttgart, 70176, Germany

Location

Medical Department I, Hospital of Barmherzige Brüder

Trier, 54292, Germany

Location

Department of Internal Medicine II, University Hospital of Tübingen

Tübingen, 72076, Germany

Location

Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen

Villingen-Schwenningen, 78050, Germany

Location

Medical Department I, Helios Hospital Wuppertal

Wuppertal, 42283, Germany

Location

Related Publications (5)

• Schlenk RF, Lubbert M, Benner A, Lamparter A, Krauter J, Herr W, Martin H, Salih HR, Kundgen A, Horst HA, Brossart P, Gotze K, Nachbaur D, Wattad M, Kohne CH, Fiedler W, Bentz M, Wulf G, Held G, Hertenstein B, Salwender H, Gaidzik VI, Schlegelberger B, Weber D, Dohner K, Ganser A, Dohner H; German-Austrian Acute Myeloid Leukemia Study Group. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Ann Hematol. 2016 Dec;95(12):1931-1942. doi: 10.1007/s00277-016-2810-z. Epub 2016 Oct 3.

  PMID: 27696203 RESULT

• Schlenk RF, Kayser S, Bullinger L, Kobbe G, Casper J, Ringhoffer M, Held G, Brossart P, Lubbert M, Salih HR, Kindler T, Horst HA, Wulf G, Nachbaur D, Gotze K, Lamparter A, Paschka P, Gaidzik VI, Teleanu V, Spath D, Benner A, Krauter J, Ganser A, Dohner H, Dohner K; German-Austrian AML Study Group. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood. 2014 Nov 27;124(23):3441-9. doi: 10.1182/blood-2014-05-578070. Epub 2014 Sep 30.

  PMID: 25270908 DERIVED

• Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Rock J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, Spath D, Kundgen A, Schmidt-Wolf IG, Gotze K, Nachbaur D, Pfreundschuh M, Horst HA, Dohner H, Dohner K. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol. 2011 Apr 1;29(10):1364-72. doi: 10.1200/JCO.2010.30.7926. Epub 2011 Feb 22.

  PMID: 21343560 DERIVED

• Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, Wittke K, Du J, Groner S, Spath D, Krauter J, Ganser A, Dohner H, Fischer T, Dohner K; German-Austrian AML Study Group (AMLSG). Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood. 2009 Sep 17;114(12):2386-92. doi: 10.1182/blood-2009-03-209999. Epub 2009 Jul 14.

  PMID: 19602710 DERIVED

• Schlenk RF, Dohner K, Kneba M, Gotze K, Hartmann F, Del Valle F, Kirchen H, Koller E, Fischer JT, Bullinger L, Habdank M, Spath D, Groner S, Krebs B, Kayser S, Corbacioglu A, Anhalt A, Benner A, Frohling S, Dohner H; German-Austrian AML Study Group (AMLSG). Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica. 2009 Jan;94(1):54-60. doi: 10.3324/haematol.13378. Epub 2008 Dec 4.

  PMID: 19059939 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Idarubicin; Etoposide; Tretinoin; pegfilgrastim

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Richard F Schlenk, Dr.

  University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr.

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: July 1, 2004
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2013
• Last Updated: September 20, 2017

Record last verified: 2017-09

Locations

DE (30); AU (4)