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

NCT ID: NCT00151242

Last Updated: 2017-09-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

920 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-07-31

Study Completion Date

2013-08-31

Brief Summary

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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).

Detailed Description

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First Induction Therapy:

* Cytarabine 100 mg/m² cont. i.v. days 1-7
* Idarubicin 12 mg/m² i.v. days 1,3,5
* Etoposide 100 mg/m² i.v. days 1-3
* ± ATRA 45 mg/m² p.o. days 6-8
* ATRA 15 mg/m² p.o. days 9-21

Second Induction Therapy:

* Cytarabine 100 mg/m² cont. i.v. days 1-7
* Idarubicin 12 mg/m² i.v. days 1 and 3
* Etoposide 100 mg/m² i.v. days 1-3
* ± ATRA 45 mg/m² p.o. days 6-8
* ATRA 15 mg/m² p.o. days 9-21

Consolidation Therapy:

cohort 1 (\<= ID 336)

* Cytarabine 3 g/m² 2x/die i.v. Tag 1,3,5
* ± ATRA 15 mg/m² p.o. Tag 6-21
* Pegfilgrastim 6 mg s.c day 10

cohort 2 (\> ID 336)

* Cytarabine 3 g/m² 2x/die i.v. Tag 1,2,3
* ± ATRA 15 mg/m² p.o. Tag 4-21
* Pegfilgrastim 6 mg s.c day 8

Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Group Type ACTIVE_COMPARATOR

Cytarabine

Intervention Type 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

Idarubicin

Intervention Type DRUG

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

Etoposide

Intervention Type DRUG

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

Pegfilgrastim

Intervention Type DRUG

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

2

Group Type EXPERIMENTAL

Cytarabine

Intervention Type 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

Idarubicin

Intervention Type DRUG

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

Etoposide

Intervention Type DRUG

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

All-trans retinoic acid

Intervention Type 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)

Pegfilgrastim

Intervention Type DRUG

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

Interventions

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Cytarabine

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

Intervention Type DRUG

Idarubicin

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

Intervention Type DRUG

Etoposide

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

Intervention Type DRUG

All-trans retinoic acid

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)

Intervention Type DRUG

Pegfilgrastim

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

Intervention Type DRUG

Other Intervention Names

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Neulasta

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Ulm

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Richard Schlenk

PD Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Richard F Schlenk, Dr.

Role: PRINCIPAL_INVESTIGATOR

University of Ulm

Locations

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Department of Hematology/Oncology, University Hospital Innsbruck

Innsbruck, , Austria

Site Status

Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern

Linz, , Austria

Site Status

Medical Department III, St. Johann-Hospital

Salzburg, , Austria

Site Status

Center of Hematology and Oncology, Hanusch-Hospital

Vienna, , Austria

Site Status

Department of General Internal Medicine, University Hospital of Bonn

Bonn, , Germany

Site Status

Medical Department I, Hospital Bremen-Mitte

Bremen, , Germany

Site Status

Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf

Düsseldorf, , Germany

Site Status

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

Essen, , Germany

Site Status

Medical Department III, Hematology/Oncology, University of Frankfurt

Frankfurt, , Germany

Site Status

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

Frankfurt, , Germany

Site Status

Internal Medicine I, University of Freiburg

Freiburg im Breisgau, , Germany

Site Status

Medical Department IV, University Hospital of Giessen

Giessen, , Germany

Site Status

Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH

Goch, , Germany

Site Status

Centre of Internal Medicine, University Hospital Göttingen

Göttingen, , Germany

Site Status

Department of Oncology and Hematology, University Hospital Eppendorf

Hamburg, , Germany

Site Status

Medical Department II, Hematology and Oncology, General Hospital Altona

Hamburg, , Germany

Site Status

Medical Department III, Clinical Center Hanau

Hanau, , Germany

Site Status

Medical Department III, Hospital Hannover-Siloah

Hanover, , Germany

Site Status

Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Department of Internal Medicine I, University Hospital of Saarland

Homburg, , Germany

Site Status

Medical Department II, City Hospital Karlsruhe gGmbH

Karlsruhe, , Germany

Site Status

Medical Department II, University Hospital of Kiel

Kiel, , Germany

Site Status

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

Lebach, , Germany

Site Status

Department of Hematology and Oncology, Hospital of Lüdenscheid

Lüdenscheid, , Germany

Site Status

Department of Hematology and Internal Oncology, University Hospital of Mainz

Mainz, , Germany

Site Status

Medical Department III, Clinical Center Rechts der Isar

München, , Germany

Site Status

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH

Oldenburg, , Germany

Site Status

Department of Hematology and Oncology, Caritas Hospital St. Theresia

Saarbrücken, , Germany

Site Status

Department of Oncology, Clinical Center of Stuttgart

Stuttgart, , Germany

Site Status

Medical Department II, Diakonie Hospital

Stuttgart, , Germany

Site Status

Medical Department I, Hospital of Barmherzige Brüder

Trier, , Germany

Site Status

Department of Internal Medicine II, University Hospital of Tübingen

Tübingen, , Germany

Site Status

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

Villingen-Schwenningen, , Germany

Site Status

Medical Department I, Helios Hospital Wuppertal

Wuppertal, , Germany

Site Status

Countries

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Austria Germany

References

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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.

Reference Type RESULT
PMID: 27696203 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25270908 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21343560 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19602710 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19059939 (View on PubMed)

Other Identifiers

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AMLSG07-04

Identifier Type: -

Identifier Source: org_study_id