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

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cytarabine
Idarubicin
Etoposide
All-trans retinoic acid
Pegfilgrastim
Sponsored by
University of Ulm
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

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 Measures

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

Full Information

First Posted
September 6, 2005
Last Updated
September 19, 2017
Sponsor
University of Ulm
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1. Study Identification

Unique Protocol Identification Number
NCT00151242
Brief Title
Study on All-Trans Retinoic Acid, Induction and Consolidation Therapy, and Pegfilgrastim After Consolidation Therapy in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia
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 Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Ulm

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
920 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Intervention Description
12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle)
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
100mg/m² i.v. day 1-3 (induction therapy)
Intervention Type
Drug
Intervention Name(s)
All-trans retinoic acid
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
Neulasta
Intervention Description
6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)
Primary Outcome Measure Information:
Title
Complete remission (CR)-rate after induction therapy
Time Frame
after the second induction cycle
Title
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
Title
Event-free survival
Time Frame
two years
Secondary Outcome Measure Information:
Title
Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs
Time Frame
during therapy
Title
Cumulative incidence of relapse
Time Frame
two years
Title
Cumulative incidence of death
Time Frame
two years
Title
Overall survival
Time Frame
two years
Title
Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle
Time Frame
during consolidation therapy
Title
Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle
Time Frame
during consolidation therapy
Title
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
Title
Days in hospital after each consolidation cycle
Time Frame
after consolidation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard F Schlenk, Dr.
Organizational Affiliation
University of Ulm
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology/Oncology, University Hospital Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern
City
Linz
ZIP/Postal Code
4010
Country
Austria
Facility Name
Medical Department III, St. Johann-Hospital
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Center of Hematology and Oncology, Hanusch-Hospital
City
Wien
ZIP/Postal Code
1140
Country
Austria
Facility Name
Department of General Internal Medicine, University Hospital of Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Medical Department I, Hospital Bremen-Mitte
City
Bremen
ZIP/Postal Code
28177
Country
Germany
Facility Name
Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden
City
Essen
ZIP/Postal Code
45239
Country
Germany
Facility Name
Medical Department III, Hematology/Oncology, University of Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst
City
Frankfurt
ZIP/Postal Code
65929
Country
Germany
Facility Name
Internal Medicine I, University of Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Medical Department IV, University Hospital of Giessen
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH
City
Goch
ZIP/Postal Code
47574
Country
Germany
Facility Name
Centre of Internal Medicine, University Hospital Göttingen
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Department of Oncology and Hematology, University Hospital Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Medical Department II, Hematology and Oncology, General Hospital Altona
City
Hamburg
ZIP/Postal Code
22763
Country
Germany
Facility Name
Medical Department III, Clinical Center Hanau
City
Hanau
ZIP/Postal Code
63450
Country
Germany
Facility Name
Medical Department III, Hospital Hannover-Siloah
City
Hannover
ZIP/Postal Code
30449
Country
Germany
Facility Name
Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Department of Internal Medicine I, University Hospital of Saarland
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Medical Department II, City Hospital Karlsruhe gGmbH
City
Karlsruhe
ZIP/Postal Code
76133
Country
Germany
Facility Name
Medical Department II, University Hospital of Kiel
City
Kiel
ZIP/Postal Code
24116
Country
Germany
Facility Name
Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach
City
Lebach
ZIP/Postal Code
66822
Country
Germany
Facility Name
Department of Hematology and Oncology, Hospital of Lüdenscheid
City
Lüdenscheid
ZIP/Postal Code
58505
Country
Germany
Facility Name
Department of Hematology and Internal Oncology, University Hospital of Mainz
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Medical Department III, Clinical Center Rechts der Isar
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany
Facility Name
Department of Hematology and Oncology, Caritas Hospital St. Theresia
City
Saarbrücken
ZIP/Postal Code
66113
Country
Germany
Facility Name
Department of Oncology, Clinical Center of Stuttgart
City
Stuttgart
ZIP/Postal Code
70174
Country
Germany
Facility Name
Medical Department II, Diakonie Hospital
City
Stuttgart
ZIP/Postal Code
70176
Country
Germany
Facility Name
Medical Department I, Hospital of Barmherzige Brüder
City
Trier
ZIP/Postal Code
54292
Country
Germany
Facility Name
Department of Internal Medicine II, University Hospital of Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen
City
Villingen-Schwenningen
ZIP/Postal Code
78050
Country
Germany
Facility Name
Medical Department I, Helios Hospital Wuppertal
City
Wuppertal
ZIP/Postal Code
42283
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
27696203
Citation
Schlenk RF, Lubbert M, Benner A, Lamparter A, Krauter J, Herr W, Martin H, Salih HR, Kundgen A, Horst HA, Brossart P, Gotze K, Nachbaur D, Wattad M, Kohne CH, Fiedler W, Bentz M, Wulf G, Held G, Hertenstein B, Salwender H, Gaidzik VI, Schlegelberger B, Weber D, Dohner K, Ganser A, Dohner H; German-Austrian Acute Myeloid Leukemia Study Group. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Ann Hematol. 2016 Dec;95(12):1931-1942. doi: 10.1007/s00277-016-2810-z. Epub 2016 Oct 3.
Results Reference
result
PubMed Identifier
25270908
Citation
Schlenk RF, Kayser S, Bullinger L, Kobbe G, Casper J, Ringhoffer M, Held G, Brossart P, Lubbert M, Salih HR, Kindler T, Horst HA, Wulf G, Nachbaur D, Gotze K, Lamparter A, Paschka P, Gaidzik VI, Teleanu V, Spath D, Benner A, Krauter J, Ganser A, Dohner H, Dohner K; German-Austrian AML Study Group. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood. 2014 Nov 27;124(23):3441-9. doi: 10.1182/blood-2014-05-578070. Epub 2014 Sep 30.
Results Reference
derived
PubMed Identifier
21343560
Citation
Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Rock J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, Spath D, Kundgen A, Schmidt-Wolf IG, Gotze K, Nachbaur D, Pfreundschuh M, Horst HA, Dohner H, Dohner 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. doi: 10.1200/JCO.2010.30.7926. Epub 2011 Feb 22.
Results Reference
derived
PubMed Identifier
19602710
Citation
Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, Wittke K, Du J, Groner S, Spath D, Krauter J, Ganser A, Dohner H, Fischer T, Dohner 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. doi: 10.1182/blood-2009-03-209999. Epub 2009 Jul 14.
Results Reference
derived
PubMed Identifier
19059939
Citation
Schlenk RF, Dohner K, Kneba M, Gotze K, Hartmann F, Del Valle F, Kirchen H, Koller E, Fischer JT, Bullinger L, Habdank M, Spath D, Groner S, Krebs B, Kayser S, Corbacioglu A, Anhalt A, Benner A, Frohling S, Dohner 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. doi: 10.3324/haematol.13378. Epub 2008 Dec 4.
Results Reference
derived

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

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