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

September 19, 2017 updated by: Prof. Dr. Richard Schlenk, University of Ulm

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

920

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Department of Hematology/Oncology, University Hospital Innsbruck
      • Linz, Austria, 4010
        • Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern
      • Salzburg, Austria, 5020
        • Medical Department III, St. Johann-Hospital
      • Wien, Austria, 1140
        • Center of Hematology and Oncology, Hanusch-Hospital
  • Germany
      • Bonn, Germany, 53127
        • Department of General Internal Medicine, University Hospital of Bonn
      • Bremen, Germany, 28177
        • Medical Department I, Hospital Bremen-Mitte
      • Düsseldorf, Germany, 40225
        • Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf
      • Essen, Germany, 45239
        • Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden
      • Frankfurt, Germany, 65929
        • Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst
      • Frankfurt, Germany, 60590
        • Medical Department III, Hematology/Oncology, University of Frankfurt
      • Freiburg, Germany, 79106
        • Internal Medicine I, University of Freiburg
      • Giessen, Germany, 35392
        • Medical Department IV, University Hospital of Gießen
      • Goch, Germany, 47574
        • Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH
      • Göttingen, Germany, 37075
        • Centre of Internal Medicine, University Hospital Göttingen
      • Hamburg, Germany, 20246
        • Department of Oncology and Hematology, University Hospital Eppendorf
      • Hamburg, Germany, 22763
        • Medical Department II, Hematology and Oncology, General Hospital Altona
      • Hanau, Germany, 63450
        • Medical Department III, Clinical Center Hanau
      • Hannover, Germany, 30449
        • Medical Department III, Hospital Hannover-Siloah
      • Hannover, Germany, 30625
        • Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover
      • Homburg, Germany, 66421
        • Department of Internal Medicine I, University Hospital of Saarland
      • Karlsruhe, Germany, 76133
        • Medical Department II, City Hospital Karlsruhe gGmbH
      • Kiel, Germany, 24116
        • Medical Department II, University Hospital of Kiel
      • Lebach, Germany, 66822
        • Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach
      • Lüdenscheid, Germany, 58505
        • Department of Hematology and Oncology, Hospital of Lüdenscheid
      • Mainz, Germany, 55101
        • Department of Hematology and internal Oncology, University Hospital of Mainz
      • München, Germany, 81675
        • Medical Department III, Clinical Center rechts der Isar
      • Oldenburg, Germany, 26133
        • Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH
      • Saarbrücken, Germany, 66113
        • Department of Hematology and Oncology, Caritas Hospital St. Theresia
      • Stuttgart, Germany, 70174
        • Department of Oncology, Clinical Center of Stuttgart
      • Stuttgart, Germany, 70176
        • Medical Department II, Diakonie Hospital
      • Trier, Germany, 54292
        • Medical Department I, Hospital of Barmherzige Brüder
      • Tübingen, Germany, 72076
        • Department of Internal Medicine II, University Hospital of Tübingen
      • Villingen-Schwenningen, Germany, 78050
        • Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen
      • Wuppertal, Germany, 42283
        • Medical Department I, Helios Hospital Wuppertal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: Pegfilgrastim
6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)
Other Names:
  • Neulasta
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)
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 Names:
  • Neulasta

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete remission (CR)-rate after induction therapy
Time Frame: after the second induction cycle
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
Time Frame: One year after consolidation therapy
One year after consolidation therapy
Event-free survival
Time Frame: two years
two years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: two years
two years
Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs
Time Frame: during therapy
during therapy
Cumulative incidence of relapse
Time Frame: two years
two years
Cumulative incidence of death
Time Frame: two years
two years
Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle
Time Frame: during consolidation therapy
during consolidation therapy
Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle
Time Frame: during consolidation therapy
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)
Time Frame: during consolidation therapy
during consolidation therapy
Days in hospital after each consolidation cycle
Time Frame: after consolidation therapy
after consolidation therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Ulm

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

September 6, 2005

First Submitted That Met QC Criteria

September 6, 2005

First Posted (Estimate)

September 8, 2005

Study Record Updates

Last Update Posted (Actual)

September 20, 2017

Last Update Submitted That Met QC Criteria

September 19, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMLSG07-04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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