Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation
1 other identifier
interventional
144
1 country
33
Brief 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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Mar 2011
Longer than P75 for phase_3
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2010
CompletedFirst Posted
Study publicly available on registry
November 10, 2010
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 13, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 13, 2018
CompletedAugust 1, 2018
July 1, 2018
7.4 years
November 9, 2010
July 31, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
overall survival
2 years and 8 months
Secondary Outcomes (11)
Rate of Complete remission
8 months
cumulative incidence of relapse
2 years and 8 months
cumulative incidence of death in complete remission
2 years and 8 months
event-free survival
2 years and 8 months
Rate of early deaths (ED)/hypoplastic deaths (HD)
8 months
- +6 more secondary outcomes
Study Arms (2)
Standard arm
ACTIVE COMPARATOR6 cycles of chemotherapy (low-dose cytarabine and etoposide) without ATRA
Investigational arm
EXPERIMENTAL6 cycles of chemotherapy (low-dose cytarabine and etoposide) with ATRA (All-trans-Retinoic acid)
Interventions
in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).
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).
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
Ubbo-Emmius Klinik Aurich
Aurich, 26603, Germany
Charité Universitätsmedizin Berlin
Berlin, 13353, Germany
University Hospital of Bonn
Bonn, 53111, Germany
Städtisches Klinikum Braunschweig
Braunschweig, 38114, Germany
Klinikum Bremen-Mitte gGmbH
Bremen, 28177, Germany
Kliniken Essen Süd, Evangelischs Krankenhaus
Essen, 45239, Germany
Klinikum Esslingen
Esslingen am Neckar, 73730, Germany
Medizinische Universitätsklinik
Freiburg im Breisgau, 79106, Germany
Medizinisches Versorgungszentrum Osthessen GmbH
Fulda, 36043, Germany
Universitätsklinikum Gießen
Giessen, 35392, Germany
Wilhelm- Anton- Hospital gGmbH
Goch, 47574, Germany
Universitätsmedizin Göttingen
Göttingen, 37075, Germany
University Hospital of Hamburg Eppendorf
Hamburg, 20246, Germany
Asklepios Klinik Altona
Hamburg, 22763, Germany
Medical Department III, Hospital of Hannover-Siloah
Hanover, 30449, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
SLK-Kliniken Heilbronn GmbH
Heilbronn, 74078, Germany
Department of Internal Medicine I, University Hospital of Saarland
Homburg, 66421, Germany
Staedtisches Klinikum Karlsruhe
Karlsruhe, 76133, Germany
Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach
Lebach, 66822, Germany
Klinikum der Johannes Gutenberg Universität Mainz
Mainz, 55131, Germany
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557, Germany
Klinikum rechts der Isar der TU Muenchen
München, 81675, Germany
Pius Hospital Oldenburg
Oldenburg, 26133, Germany
Krankenhaus der Barmherzigen Brueder
Regensburg, 93049, Germany
Caritas-Klinik St. Theresia
Saarbrücken, 66113, Germany
Clinikal Cetner of Stuttgart, Center of Oncology
Stuttgart, 70174, Germany
Diakonie-Klinikum Stuttgart
Stuttgart, 70176, Germany
Krankenhaus der Barmherzigen Brüder Trier
Trier, 54292, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
University hospital of Ulm
Ulm, 89081, Germany
Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen
Villingen-Schwenningen, 78050, Germany
Helios Klinikum Wuppertal
Wuppertal, 42283, Germany
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hartmut Döhner, MD
University Hospital of Ulm
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr.
Study Record Dates
First Submitted
November 9, 2010
First Posted
November 10, 2010
Study Start
March 1, 2011
Primary Completion
July 13, 2018
Study Completion
July 13, 2018
Last Updated
August 1, 2018
Record last verified: 2018-07