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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00151242
• Other study ID #: AMLSG07-04
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 6, 2005
• Last updated: September 19, 2017
• Start date: July 2004
• Est. completion date: August 2013

Study information

• Verified date: September 2017
• Source: University of Ulm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 920
• Est. completion date: August 2013
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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
• Idarubicin
12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle)
• Etoposide
100mg/m² i.v. day 1-3 (induction therapy)
• 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)
• Pegfilgrastim
6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)

Locations

Country	Name	City	State
Austria	Department of Hematology/Oncology, University Hospital Innsbruck	Innsbruck
Austria	Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern	Linz
Austria	Medical Department III, St. Johann-Hospital	Salzburg
Austria	Center of Hematology and Oncology, Hanusch-Hospital	Wien
Germany	Department of General Internal Medicine, University Hospital of Bonn	Bonn
Germany	Medical Department I, Hospital Bremen-Mitte	Bremen
Germany	Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf	Düsseldorf
Germany	Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden	Essen
Germany	Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst	Frankfurt
Germany	Medical Department III, Hematology/Oncology, University of Frankfurt	Frankfurt
Germany	Internal Medicine I, University of Freiburg	Freiburg
Germany	Medical Department IV, University Hospital of Giessen	Giessen
Germany	Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH	Goch
Germany	Centre of Internal Medicine, University Hospital Göttingen	Göttingen
Germany	Department of Oncology and Hematology, University Hospital Eppendorf	Hamburg
Germany	Medical Department II, Hematology and Oncology, General Hospital Altona	Hamburg
Germany	Medical Department III, Clinical Center Hanau	Hanau
Germany	Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover	Hannover
Germany	Medical Department III, Hospital Hannover-Siloah	Hannover
Germany	Department of Internal Medicine I, University Hospital of Saarland	Homburg
Germany	Medical Department II, City Hospital Karlsruhe gGmbH	Karlsruhe
Germany	Medical Department II, University Hospital of Kiel	Kiel
Germany	Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach	Lebach
Germany	Department of Hematology and Oncology, Hospital of Lüdenscheid	Lüdenscheid
Germany	Department of Hematology and Internal Oncology, University Hospital of Mainz	Mainz
Germany	Medical Department III, Clinical Center Rechts der Isar	München
Germany	Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH	Oldenburg
Germany	Department of Hematology and Oncology, Caritas Hospital St. Theresia	Saarbrücken
Germany	Department of Oncology, Clinical Center of Stuttgart	Stuttgart
Germany	Medical Department II, Diakonie Hospital	Stuttgart
Germany	Medical Department I, Hospital of Barmherzige Brüder	Trier
Germany	Department of Internal Medicine II, University Hospital of Tübingen	Tübingen
Germany	Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen	Villingen-Schwenningen
Germany	Medical Department I, Helios Hospital Wuppertal	Wuppertal

Sponsors (1)

Lead Sponsor	Collaborator
University of Ulm

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (1)

Schlenk RF, Lübbert M, Benner A, Lamparter A, Krauter J, Herr W, Martin H, Salih HR, Kündgen A, Horst HA, Brossart P, Götze K, Nachbaur D, Wattad M, Köhne CH, Fiedler W, Bentz M, Wulf G, Held G, Hertenstein B, Salwender H, Gaidzik VI, Schlegelberger B, We — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission (CR)-rate after induction therapy		after the second induction cycle
Primary	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
Primary	Event-free survival		two years
Secondary	Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs		during therapy
Secondary	Cumulative incidence of relapse		two years
Secondary	Cumulative incidence of death		two years
Secondary	Overall survival		two years
Secondary	Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle		during consolidation therapy
Secondary	Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle		during consolidation therapy
Secondary	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)		during consolidation therapy
Secondary	Days in hospital after each consolidation cycle		after consolidation therapy

External Links

•   AMLSG Study Office, Department of Internal Medicine III, University of Ulm