Clinical trial NCT01237808: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia (AML)
Keywords: AML
NPM1 Mutation
elderly patients (>60 years)
unfit for intensive chemotherapy
Lead sponsor: University of Ulm
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2010-11-10
Enrollment: 144
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: overall survival
timeFrame: 2 years and 8 months
Secondary outcomes:
measure: Rate of Complete remission
timeFrame: 8 months
measure: cumulative incidence of relapse
timeFrame: 2 years and 8 months
measure: cumulative incidence of death in complete remission
timeFrame: 2 years and 8 months
measure: event-free survival
timeFrame: 2 years and 8 months
measure: Rate of early deaths (ED)/hypoplastic deaths (HD)
timeFrame: 8 months
measure: Type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles
timeFrame: 8 months
measure: Incidence of infection after each treatment cycle
timeFrame: 8 months
measure: Duration of neutropenia after each treatment cycle
timeFrame: 8 months
measure: Duration of thrombocytopenia after each treatment cycle
timeFrame: 8 months
measure: Duration of hospitalization after each treatment cycle
timeFrame: 8 months
measure: Quality of life
timeFrame: 2 years and 8 months
Other outcomes:
Locations:
city: Aurich
country: Germany
facility: Ubbo-Emmius Klinik Aurich
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: University Hospital of Bonn
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte gGmbH
city: Essen
country: Germany
facility: Kliniken Essen Süd, Evangelischs Krankenhaus
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Freiburg
country: Germany
facility: Medizinische Universitätsklinik
city: Fulda
country: Germany
facility: Medizinisches Versorgungszentrum Osthessen GmbH
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen
city: Goch
country: Germany
facility: Wilhelm- Anton- Hospital gGmbH
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: University Hospital of Hamburg Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hannover
country: Germany
facility: Medical Department III, Hospital of Hannover-Siloah
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Homburg
country: Germany
facility: Department of Internal Medicine I, University Hospital of Saarland
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe
city: Lebach
country: Germany
facility: Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg Universität Mainz
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
city: Regensburg
country: Germany
facility: Krankenhaus der Barmherzigen Brueder
city: Saarbrücken
country: Germany
facility: Caritas-Klinik St. Theresia
city: Stuttgart
country: Germany
facility: Clinikal Cetner of Stuttgart, Center of Oncology
city: Stuttgart
country: Germany
facility: Diakonie-Klinikum Stuttgart
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder Trier
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: University hospital of Ulm
city: Villingen - Schwenningen
country: Germany
facility: Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
Study officials:
affiliation: University Hospital of Ulm
name: Hartmut Döhner, MD
role: PRINCIPAL_INVESTIGATOR
References: