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

Sponsor:	University of Ulm
Information provided by (Responsible Party):	Dr. Richard Schlenk, University of Ulm
ClinicalTrials.gov Identifier:	NCT00151242

Purpose

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).

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Cytarabine Drug: Idarubicin Drug: Etoposide Drug: All-trans retinoic acid Drug: Pegfilgrastim	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Phase II/III-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

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Cytarabine hydrochloride Etoposide Idarubicin hydrochloride Idarubicin Etoposide phosphate Pegfilgrastim Cytarabine Tretinoin

U.S. FDA Resources

Further study details as provided by University of Ulm:

Primary Outcome Measures:

Complete remission (CR)-rate after induction therapy [ Time Frame: after the second induction cycle ] [ Designated as safety issue: No ]
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 [ Time Frame: One year after consolidation therapy ] [ Designated as safety issue: No ]
Event-free survival [ Time Frame: two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs [ Time Frame: during therapy ] [ Designated as safety issue: No ]
Cumulative incidence of relapse [ Time Frame: two years ] [ Designated as safety issue: No ]
Cumulative incidence of death [ Time Frame: two years ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: two years ] [ Designated as safety issue: No ]
Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle [ Time Frame: during consolidation therapy ] [ Designated as safety issue: Yes ]
Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle [ Time Frame: during consolidation therapy ] [ Designated as safety issue: No ]
Hematologic and non-hematologic toxicity after consolidation therapy with high-dose cytarabine considering the different consolidation schemes (day 1-3-5 versus day 1-2-3) [ Time Frame: during consolidation therapy ] [ Designated as safety issue: Yes ]
Days in hospital after each consolidation cycle [ Time Frame: after consolidation therapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	920
Study Start Date:	July 2004
Estimated Study Completion Date:	February 2012
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1	Drug: 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 Drug: Idarubicin 12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle) Drug: Etoposide 100mg/m² i.v. day 1-3 (induction therapy) Drug: Pegfilgrastim 6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2) Other Name: Neulasta
Experimental: 2	Drug: 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 Drug: Idarubicin 12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle) Drug: Etoposide 100mg/m² i.v. day 1-3 (induction therapy) 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) Drug: Pegfilgrastim 6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2) Other Name: Neulasta

Arms

Assigned Interventions

Active Comparator: 1

Drug: 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

Drug: Idarubicin

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

Drug: Etoposide

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

Drug: Pegfilgrastim

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

Other Name: Neulasta

Experimental: 2

Drug: 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

Drug: Idarubicin

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

Drug: Etoposide

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

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)

Drug: Pegfilgrastim

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

Other Name: Neulasta

Detailed Description:

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

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00151242

Locations

Austria
Department of Hematology/Oncology, University Hospital 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 General Internal Medicine, University Hospital of Bonn
Bonn, Germany, 53127
Medical Department I, Hospital Bremen-Mitte
Bremen, Germany, 28177
Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf
Düsseldorf, Germany, 40225
Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden
Essen, Germany, 45239
Medical Department III, Hematology/Oncology, University of Frankfurt
Frankfurt, Germany, 60590
Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst
Frankfurt, Germany, 65929
Internal Medicine I, University of Freiburg
Freiburg, Germany, 79106
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 Göttingen
Göttingen, Germany, 37075
Medical Department II, Hematology and Oncology, General Hospital Altona
Hamburg, Germany, 22763
Department of Oncology and Hematology, University Hospital Eppendorf
Hamburg, Germany, 20246
Medical Department III, Clinical Center Hanau
Hanau, Germany, 63450
Medical Department III, Hospital Hannover-Siloah
Hannover, Germany, 30449
Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover
Hannover, Germany, 30625
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, Cartias Hospital Lebach
Lebach, Germany, 66822
Department of Hematology and Oncology, Hospital of Lüdenscheid
Lüdenscheid, Germany, 58505
Department of Hematology and Internal Oncology, University Hospital of Mainz
Mainz, Germany, 55101
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. Theresia
Saarbrücken, Germany, 66113
Department of Oncology, Clinical Center of Stuttgart
Stuttgart, Germany, 70174
Medical Department II, Diakonie Hospital
Stuttgart, Germany, 70176
Medical Department I, Hospital of Barmherzige Brüder
Trier, Germany, 54292
Department of Internal Medicine II, University Hospital of Tübingen
Tübingen, Germany, 72076
Medical Clinic II-Hematology/Oncology, Hospital 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

Additional Information:

AMLSG Study Office, Department of Internal Medicine III, University of Ulm This link exits the ClinicalTrials.gov site

No publications provided by University of Ulm

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

Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Röck J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, Späth D, Kündgen A, Schmidt-Wolf IG, Götze K, Nachbaur D, Pfreundschuh M, Horst HA, Döhner H, Döhner 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. Epub 2011 Feb 22.

Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, Wittke K, Du J, Groner S, Späth D, Krauter J, Ganser A, Döhner H, Fischer T, Döhner 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. Epub 2009 Jul 14.

Schlenk RF, Döhner K, Kneba M, Götze K, Hartmann F, Del Valle F, Kirchen H, Koller E, Fischer JT, Bullinger L, Habdank M, Späth D, Groner S, Krebs B, Kayser S, Corbacioglu A, Anhalt A, Benner A, Fröhling S, Döhner 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. Epub 2008 Dec 4.

Responsible Party:	Dr. Richard Schlenk, PD Dr., University of Ulm
ClinicalTrials.gov Identifier:	NCT00151242 History of Changes
Other Study ID Numbers:	AMLSG07-04
Study First Received:	September 6, 2005
Last Updated:	October 12, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Etoposide
Idarubicin
Tretinoin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antibiotics, Antineoplastic
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on February 09, 2012