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

Condition(s) targeted: Acute Myeloid Leukemia

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

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: University of Ulm

Official(s) and/or principal investigator(s):
Richard F Schlenk, Dr., Principal Investigator, Affiliation: Department of Internal Medicine III, University of Ulm

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).

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Complete remission (CR)-rate after induction therapy

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

Event-free survival

Secondary outcome:

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

Cumulative incidence of relapse

Cumulative incidence of death

Overall survival

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

Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle

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)

Days in hospital after each consolidation cycle

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

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

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

Department of Hematology/Oncology, University Hospital Innsbruck, Innsbruck 6020, Austria

Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern, Linz 4010, Austria

Medical Department III, St. Johann-Hospital, Salzburg 5020, Austria

Center of Hematology and Oncology, Hanusch-Hospital, Wien 1140, Austria

Department of General Internal Medicine, University Hospital of Bonn, Bonn 53127, Germany

Medical Department I, Hospital Bremen-Mitte, Bremen 28177, Germany

Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf, Düsseldorf 40225, Germany

Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden, Essen 45239, Germany

Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst, Frankfurt 65929, Germany

Medical Department III, Hematology/Oncology, University of Frankfurt, Frankfurt 60590, Germany

Internal Medicine I, University of Freiburg, Freiburg 79106, Germany

Medical Department IV, University Hospital of Giessen, Giessen 35392, Germany

Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH, Goch 47574, Germany

Centre of Internal Medicine, University Hospital Göttingen, Göttingen 37075, Germany

Department of Oncology and Hematology, University Hospital Eppendorf, Hamburg 20246, Germany

Medical Department II, Hematology and Oncology, General Hospital Altona, Hamburg 22763, Germany

Medical Department III, Clinical Center Hanau, Hanau 63450, Germany

Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover, Hannover 30625, Germany

Medical Department III, Hospital Hannover-Siloah, Hannover 30449, Germany

Department of Internal Medicine I, University Hospital of Saarland, Homburg 66421, Germany

Medical Department II, City Hospital Karlsruhe gGmbH, Karlsruhe 76133, Germany

Medical Department II, University Hospital of Kiel, Kiel 24116, Germany

Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach, Lebach 66822, Germany

Department of Hematology and Oncology, Hospital of Lüdenscheid, Lüdenscheid 58505, Germany

Department of Hematology and Internal Oncology, University Hospital of Mainz, Mainz 55101, Germany

Medical Department III, Clinical Center Rechts der Isar, München 81675, Germany

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH, Oldenburg 26133, Germany

Department of Hematology and Oncology, Caritas Hospital St. Theresia, Saarbrücken 66113, Germany

Department of Oncology, Clinical Center of Stuttgart, Stuttgart 70174, Germany

Medical Department II, Diakonie Hospital, Stuttgart 70176, Germany

Medical Department I, Hospital of Barmherzige Brüder, Trier 54292, Germany

Department of Internal Medicine II, University Hospital of Tübingen, Tübingen 72076, Germany

Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen, Villingen-Schwenningen 78050, Germany

Medical Department I, Helios Hospital Wuppertal, Wuppertal 42283, Germany

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

Starting date: July 2004
Last updated: July 22, 2014