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

Phase 2

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Cytarabine; Drug: Idarubicin; Drug: Etoposide; Drug: Pegfilgrastim; Drug: All-trans retinoic acid

• Registration Number: NCT00151242
• Lead Sponsor: University of Ulm

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).

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

Study Timeline

• Study Start: 2004-07
• Study First Submitted: 2005-09-06
• Study First Submitted QC: 2005-09-06
• Study First Posted: 2005-09-08
• Primary Completion: 2011-08
• Study Completion: 2013-08
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-19
• Last Update Posted: 2017-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 920

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Pegfilgrastim	-
1	Idarubicin	-
1	Etoposide	-
1	Cytarabine	-
2	Pegfilgrastim	-
2	All-trans retinoic acid	-
2	Cytarabine	-
2	Idarubicin	-
2	Etoposide	-

Primary Outcome Measures

Name	Time	Method
Event-free survival	two years
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

Secondary Outcome Measures

Name	Time	Method
Overall survival	two years
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
Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle	during consolidation therapy
Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle	during consolidation therapy
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
Days in hospital after each consolidation cycle	after consolidation therapy

Trial Locations

Locations (34)

Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf; 🇩🇪 Düsseldorf, Germany

Department of Hematology/Oncology, University Hospital Innsbruck; 🇦🇹 Innsbruck, Austria

Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden; 🇩🇪 Essen, Germany

Internal Medicine I, University of Freiburg; 🇩🇪 Freiburg, Germany

Medical Department III, St. Johann-Hospital; 🇦🇹 Salzburg, Austria

Medical Department III, Hospital Hannover-Siloah; 🇩🇪 Hannover, Germany

Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Medical Department II, Hematology and Oncology, General Hospital Altona; 🇩🇪 Hamburg, Germany

Medical Department II, Diakonie Hospital; 🇩🇪 Stuttgart, Germany

Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen; 🇩🇪 Villingen-Schwenningen, Germany

Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern; 🇦🇹 Linz, Austria

Center of Hematology and Oncology, Hanusch-Hospital; 🇦🇹 Wien, Austria

Department of General Internal Medicine, University Hospital of Bonn; 🇩🇪 Bonn, Germany

Medical Department III, Hematology/Oncology, University of Frankfurt; 🇩🇪 Frankfurt, Germany

Medical Department I, Hospital Bremen-Mitte; 🇩🇪 Bremen, Germany

Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst; 🇩🇪 Frankfurt, Germany

Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH; 🇩🇪 Goch, Germany

Medical Department IV, University Hospital of Giessen; 🇩🇪 Giessen, Germany

Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach; 🇩🇪 Lebach, Germany

Medical Department II, City Hospital Karlsruhe gGmbH; 🇩🇪 Karlsruhe, Germany

Medical Department III, Clinical Center Rechts der Isar; 🇩🇪 München, Germany

Medical Department III, Clinical Center Hanau; 🇩🇪 Hanau, Germany

Department of Oncology and Hematology, University Hospital Eppendorf; 🇩🇪 Hamburg, Germany

Centre of Internal Medicine, University Hospital Göttingen; 🇩🇪 Göttingen, Germany

Medical Department II, University Hospital of Kiel; 🇩🇪 Kiel, Germany

Department of Hematology and Oncology, Caritas Hospital St. Theresia; 🇩🇪 Saarbrücken, 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 I, Helios Hospital Wuppertal; 🇩🇪 Wuppertal, Germany

Department of Oncology, Clinical Center of Stuttgart; 🇩🇪 Stuttgart, Germany

Medical Department I, Hospital of Barmherzige Brüder; 🇩🇪 Trier, Germany

Department of Internal Medicine II, University Hospital of Tübingen; 🇩🇪 Tübingen, Germany

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH; 🇩🇪 Oldenburg, Germany

Department of Internal Medicine I, University Hospital of Saarland; 🇩🇪 Homburg, Germany