Clinical trial NCT01180322: Trial Evaluating Induction Therapy With Idarubicin and Etoposide Plus Sequential or Concurrent Azacitidine and Maintenance Therapy With Azacitidine
Official title: Randomized Phase-II Trial Evaluating Induction Therapy With Idarubicin and Etoposide Plus Sequential or Concurrent Azacitidine and Maintenance Therapy With Azacitidine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: azacitidine
Acute myeloid Leukemia (AML)
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2010-08-12
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized phase II, four-arm, open-label, multi-center study in adult patients with acute myeloid leukemia (AML) as defined in inclusion/exclusion criteria.

The primary efficacy objective is to evaluate the impact of sequential or concurrent addition of 5-azacytidine to intensive induction chemotherapy with idarubicin and etoposide on the complete remission (CR) rate

Sample size: 336 patients

The treatment duration of an individual patient randomized into one of the three experimental arms (Arm B, C, D) (in case of application of induction, consolidation and maintenance therapy with Azacitidine) is about 30 months.

The treatment duration for patients randomized into the standard arm of the study (Arm A) is about 7 months (in case of application of induction, consolidation and 2-yrs observation as maintenance (without treatment with Azacitidine)).

In case of induction followed by consolidation with allogeneic Stem cell transplantation (SCT) the treatment duration per patient is about 6 months.

Every patient will be followed until month 54 after inclusion into the study. Duration of the study for an individual patient including treatment (induction, consolidation \[chemotherapy or allogeneic SCT\], maintenance \[experimental arm with Azacitidine or observation\]) and follow-up period: 54 months


Eligibility criteria: Inclusion Criteria:

* Patients with suspected diagnosis of acute myeloid leukemia or related precursor neoplasm, or acute leukemia of ambiguous lineage (classified according to the World Health Organization (WHO) classification)
* Patients considered eligible for intensive chemotherapy
* WHO performance status of ≤ 2
* Age ≥ 18 years. There is no upper age limit.
* No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis
* Non-pregnant and non-nursing. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.
* Female patients in the reproductive age and male patients must agree to avoid getting pregnant or to father a child while on therapy and for 3 month after the last dose of chemotherapy.
* Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy). Hormonal contraception is an inadequate method of birth control.
* Men 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)
* Signed written informed consent.

Exclusion Criteria:

-AML with other recurrent genetic abnormalities (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 variant translocations with other RARA gene fusions)

* AML with NPM1 mutation
* AML with FLT3 mutation
* Performance status WHO \>2
* Patients with ejection fraction \< 50% by Multi Gated Acquisition Scan (MUGA) or echocardiogram (ECHO scan) within 14 days of day 1
* 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)
* Uncontrolled infection
* 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.
* Known positive for Human immunodeficiency virus (HIV)
* Bleeding disorder independent of leukemia
* No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and/or other physicians involved in the treatment of the patient about study participation.
* No consent for biobanking.

Primary outcomes:
measure: Rates of complete remission (CR) after induction therapy
timeFrame: 56 days
Secondary outcomes:
measure: Event-free survival
timeFrame: after two years of follow-up
measure: Relapse-free survival
timeFrame: after two years of follow-up
measure: overall survival
timeFrame: after two years of follow-up
measure: days in hospital during each cycle and during the whole intervention
timeFrame: 6 months
measure: Rate of early deaths or hypoplastic deaths (ED/HD)
timeFrame: 56 days
measure: type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of non-hematological toxicity observed during different treatment cycles
timeFrame: 6 months
measure: quality of life assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30)
timeFrame: at the end of therapy (in average 6 months) and once a year in the follow-up
measure: duration of leukopenia after each consolidation cycle
timeFrame: 42 days
measure: duration of neutropenia after each consolidation cycle
timeFrame: 42 days
measure: duration of thrombocytopenia after each consolidation cycle
timeFrame: 42 days
measure: duration of leukopenia after each induction cycle
timeFrame: 28 days
measure: duration of neutropenia after each induction cycle
timeFrame: 28 days
measure: duration of thrombocytopenia after each induction cycle
timeFrame: 28 days
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Universitätsklinikum Innsbruck
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Schwestern
city: Linz
country: Austria
facility: Elisabethinen Krankenhaus Linz
city: Salzburg
country: Austria
facility: Landeskliniken Salzburg
city: Wien
country: Austria
facility: Hanuschkrankenhaus
city: Berlin
country: Germany
facility: Universitätsklinikum Charité Berlin
city: Bochum
country: Germany
facility: Knappschaftskrankenhaus Bochum-Langendreer
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Kliniken Essen Süd, Evangelischs Krankenhaus
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt-Höchst
city: Fulda
country: Germany
facility: Medizinisches Versorgungszentrum Fulda
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen
city: Goch
country: Germany
facility: Wilhelm-Anton-Hospital Goch
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Hamburg
country: Germany
facility: Sklepios Klinik Hamburg-Altona
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm
city: Hanau
country: Germany
facility: Klinikum Hanau
city: Hannover
country: Germany
facility: KRH Klinikum Hannover-Siloah
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Lebach
country: Germany
facility: Caritas-Krankenhaus Lebach
city: Lemgo
country: Germany
facility: Klinikum Lippe
city: Lüdenscheid
country: Germany
facility: Klinikum Lüdenscheid
city: Mainz
country: Germany
facility: Klinikum der Johannes-Guttenberg-Universität
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch-Gmünd
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Passau
country: Germany
facility: Klinikum Passau
city: Regensburg
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: Saarbrücken
country: Germany
facility: Caritas-Klinik St. Theresia
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Diakonie-Klinikum Stuttgart
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar-Klinikum
city: Wuppertal
country: Germany
facility: Helios Klinikum
Study officials:
affiliation: University Hospital of Ulm
name: Richard F Schlenk, MD
role: PRINCIPAL_INVESTIGATOR
References: