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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01237808
Other study ID # AMLSG 15-10
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date March 2011
Est. completion date July 13, 2018

Study information

Verified date July 2018
Source University of Ulm
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a randomized, Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation ineligible for intensive chemotherapy.

Sample size: 144 patients

Investigator's sites: 50-55 sites in Germany and Austria (2-10 patients per trial site are expected to be included into the trial)

Estimated treatment duration of an individual patient: 8 months (Follow-Up period per patient will last additional 2 years)


Recruitment information / eligibility

Status Completed
Enrollment 144
Est. completion date July 13, 2018
Est. primary completion date July 13, 2018
Accepts healthy volunteers No
Gender All
Age group 61 Years and older
Eligibility Inclusion Criteria:

- Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification (including de novo AML, t-AML and s-AML)

- Presence of NPM1 mutation as assessed in one of the central AMLSG reference laboratories.

- Age > 60 years. There is no upper age limit.

- No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 10 days during the diagnostic screening phase.

- Signed written informed consent

- Men must give their informed consent that they do not father a baby and must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. (while on therapy and for 3 month after the last dose of chemotherapy)

- WHO performance status = 3

- Patients not eligible for intensive chemotherapy according to at least one of the following criteria

- HCT-CI Score >2

- Patient's decision

- age = 75 years

Exclusion Criteria:

The presence of any of the following will exclude a patient from study enrollment:

- All other AML subtypes, in particular those AML with other recurrent genetic changes (according to WHO 2008):

- AML with t(8;21)(q22;q22); RUNX1-RUNX1T1

- AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

- AML with t(15;17)(q22;q12); PML-RARA (or other translocations involving RARA)

- AML with t(9;11)(p22;q23); MLLT3-MLL (or other translocations involving MLL)

- AML with t(6;9)(p23;q34); DEK-NUP214

- AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

- No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and all other treating physicians about study participation

- Bleeding disorder independent of leukemia

- Uncontrolled infection

- Known positive for HIV, HBV or HCV

- Organ insufficiency (creatinine >1.5x upper normal serum level; bilirubin, AST or ALP >2.5x upper normal serum level, not attributable to AML; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)

- Severe neurological or psychiatric disorder interfering with ability of giving an informed consent

- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.

Study Design


Intervention

Drug:
Cytarabine
in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).
Etoposide
first treatment cycle Etoposide 50 mg/m²/day, continuously i.v., days 1-3; (total dose 150 mg/m2) treatment cycles 2 to 6 Etoposide 100 mg/day, p.o. or i.v. (over 1 hour), days 1-3; (total dose 300 mg).
All-trans retinoic acid (ATRA)
in all treatment cycles: ATRA 45 mg/m²/day p.o., days 8-10, ATRA 15 mg/m²/day p.o., days 11-28, with or shortly after meals distributed on 3 doses per day.

Locations

Country Name City State
Germany Ubbo-Emmius Klinik Aurich Aurich
Germany Charité Universitätsmedizin Berlin Berlin
Germany University Hospital of Bonn Bonn
Germany Städtisches Klinikum Braunschweig Braunschweig
Germany Klinikum Bremen-Mitte gGmbH Bremen
Germany Kliniken Essen Süd, Evangelischs Krankenhaus Essen
Germany Klinikum Esslingen Esslingen
Germany Medizinische Universitätsklinik Freiburg
Germany Medizinisches Versorgungszentrum Osthessen GmbH Fulda
Germany Universitätsklinikum Gießen Gießen
Germany Wilhelm- Anton- Hospital gGmbH Goch
Germany Universitätsmedizin Göttingen Göttingen
Germany Asklepios Klinik Altona Hamburg
Germany University Hospital of Hamburg Eppendorf Hamburg
Germany Medical Department III, Hospital of Hannover-Siloah Hannover
Germany Medizinische Hochschule Hannover Hannover
Germany SLK-Kliniken Heilbronn GmbH Heilbronn
Germany Department of Internal Medicine I, University Hospital of Saarland Homburg
Germany Staedtisches Klinikum Karlsruhe Karlsruhe
Germany Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach Lebach
Germany Klinikum der Johannes Gutenberg Universität Mainz Mainz
Germany Klinikum rechts der Isar der TU Muenchen Muenchen
Germany Stauferklinikum Schwäbisch Gmünd Mutlangen
Germany Pius Hospital Oldenburg Oldenburg
Germany Krankenhaus der Barmherzigen Brueder Regensburg
Germany Caritas-Klinik St. Theresia Saarbrücken
Germany Clinikal Cetner of Stuttgart, Center of Oncology Stuttgart
Germany Diakonie-Klinikum Stuttgart Stuttgart
Germany Krankenhaus der Barmherzigen Brüder Trier Trier
Germany Universitätsklinikum Tübingen Tübingen
Germany University hospital of Ulm Ulm
Germany Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen Villingen - Schwenningen
Germany Helios Klinikum Wuppertal Wuppertal

Sponsors (2)

Lead Sponsor Collaborator
University of Ulm German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary overall survival 2 years and 8 months
Secondary Rate of Complete remission 8 months
Secondary cumulative incidence of relapse 2 years and 8 months
Secondary cumulative incidence of death in complete remission 2 years and 8 months
Secondary event-free survival 2 years and 8 months
Secondary Rate of early deaths (ED)/hypoplastic deaths (HD) 8 months
Secondary Type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.0 8 months
Secondary Incidence of infection after each treatment cycle 8 months
Secondary Duration of neutropenia after each treatment cycle 8 months
Secondary Duration of thrombocytopenia after each treatment cycle 8 months
Secondary Duration of hospitalization after each treatment cycle 8 months
Secondary Quality of life assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics according to Messerer et al.33 2 years and 8 months
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