Protocol in Acute Myeloid Leukemia With FLT3-ITD
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT01477606
- Lead Sponsor
- University of Ulm
- Brief Summary
This is a phase II, single-arm, open-label, multi-center study in adult patients with Acute Myeloid Leukemia (AML) and FLT3-ITD as defined in inclusion/exclusion criteria.
The primary efficacy object is to evaluate the impact of midostaurin given in combination with intensive induction, consolidation including allogeneic hematopoietic stem cell transplantation and single agent maintenance therapy on event-free survival (EFS) in adult patients with AML exhibiting a FLT3-ITD.
Sample size: 440 patients
The treatment duration of an individual patient is between 18 and 24 months. Duration of the study for an individual patient including treatment (induction, consolidation \[chemotherapy or allogeneic SCT\], maintenance and follow-up period: Maximum 8 years
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 451
- Patients with suspected diagnosis of AML or related precursor neoplasm, or acute leukemia of ambiguous lineage (classified according to the World Health Organization (WHO) 2008 classification)
- Presence of FLT3-ITD assessed in the central AMLSG reference laboratories
- Patients considered eligible for intensive chemotherapy
- WHO performance status of ≤ 2
- Age ≥ 18 years and ≤ 70 years
- No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis (≤ 7 days)
- 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 5 months 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 5 months after the last dose of chemotherapy)
- Signed written informed consent.
•AML with the following 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)
- Performance status WHO >2
- Patients with ejection fraction < 50% by MUGA or 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 HIV; active HBV, HCV, or Hepatitis A infection
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Midostaurin Midostaurin - Midostaurin Cytarabine - Midostaurin Daunorubicin -
- Primary Outcome Measures
Name Time Method Event-free Survival 8years To perform two predefined subgroup analyses in the age-groups 18-60 years and 61-70 years evaluating the impact of midostaurin given in combination with intensive induction, consolidation including allogeneic hematopoietic stem cell transplantation and single agent maintenance therapy on event-free survival (EFS) in adult patients with AML exhibiting a FLT3-ITD.
- Secondary Outcome Measures
Name Time Method overall survival 8 years cumulative incidence of death in CR 8 years Target (FLT3) inhibition by measuring the FLT3 plasma inhibitory activity 8 years Evaluation of target (FLT3) inhibition by continuous dosing of midostaurin
Rate of early deaths and hypoplastic deaths (ED/HD) two months Rate of complete remission (CR) Two months Cumulative incidence of relapse 8 years Quality of life 5 years 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 initially, in first CR, after one year,3 and 5 years after initial diagnosis.
Death in CR 8 years Impact of allogeneic HSCT 8 years Assessment of the relative impact of allogeneic HSCT analyzed as time-dependent variable on survival endpoints.
Relapse-free survival 8 years Toxicities between 18 and 24 months Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 3.0), timing and relatedness of hematological and non-hematological toxicities observed during the different treatment cycles
Trial Locations
- Locations (55)
Krankenhaus der Elisabethinen Linz GmbH
🇦🇹Linz, Austria
Helios Klinikum Bad Saarow
🇩🇪Bad Saarow, Germany
Städtisches Klinikum Braunschweig gGmbH
🇩🇪Braunschweig, Germany
Vivantes Klinikum Neukölln
🇩🇪Berlin, Germany
Medizinische Universitätsklinik Bochum
🇩🇪Bochum, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Klinikum Bremen-Mitte gGmbH
🇩🇪Bremen, Germany
Klinikum Darmstadt
🇩🇪Darmstadt, Germany
Klinik für Onkologie, Gastroenterologie und Allg. Innere Medizin Esslingen
🇩🇪Esslingen, Germany
Kliniken Essen-Süd
🇩🇪Essen, Germany
Universitätsklinkum Düsseldorf
🇩🇪Düsseldorf, Germany
MVZ Osthessen
🇩🇪Fulda, Germany
Malteser Krankenhaus St. Franziskus Hospital Flensburg
🇩🇪Flensburg, Germany
Medizinische Universitätsklinik Freiburg
🇩🇪Freiburg, Germany
Wilhelm-Anton-Hospital gGmbH Goch
🇩🇪Goch, Germany
Klinik der Justus-Liebig-Universität Gießen
🇩🇪Gießen, Germany
Universitätsklinikum Eppendorf
🇩🇪Hamburg, Germany
Evangelisches Krankenhaus Hamm
🇩🇪Hamm, Germany
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Klinikum Region Hannover GmbH
🇩🇪Hannover, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätskliniken des Saarlandes
🇩🇪Homburg/Saar, Germany
SLK Kliniken Heilbronn GmbH
🇩🇪Heilbronn, Germany
Städtisches Klinikum Karlsruhe
🇩🇪Karlsruhe, Germany
Städtisches Krankenhaus Kiel GmbH
🇩🇪Kiel, Germany
Klinikum Lippe-Lemgo
🇩🇪Lemgo, Germany
Caritas Krankenhaus Lebach
🇩🇪Lebach, Germany
Märkische Kliniken GmbH Lüdenscheid
🇩🇪Lüdenscheid, Germany
Universitätsklinikum der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Universitätsklinikum der Otto-von-Guericke Universität Magdeburg
🇩🇪Magdeburg, Germany
Stauferklinikum Mutlangen
🇩🇪Mutlangen, Germany
Klinikum Schwabing
🇩🇪München, Germany
Klinikum rechts der Isar der TU München
🇩🇪München, Germany
Pius Hospital Oldenburg
🇩🇪Oldenburg, Germany
Ortenau Klinikum
🇩🇪Offenburg, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Klinikum Passau
🇩🇪Passau, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Caritasklinik St. Theresia Saarbrücken
🇩🇪Saarbrücken, Germany
Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Krankenhaus der Barmherzigen Brüder Trier
🇩🇪Trier, Germany
Diakonie-Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Medizinische Universitätsklinik Tübingen
🇩🇪Tübingen, Germany
Klinikum Mutterhaus der Borromäerinnen gGmbH Trier
🇩🇪Trier, Germany
Schwarzwald-Baar Klinikum Villingen-Schwenningen
🇩🇪Villingen-Schwenningen, Germany
University Hospital of Ulm
🇩🇪Ulm, Germany
Helios Klinikum Wuppertal
🇩🇪Wuppertal, Germany
Universitätsklinik für Innere Medizin III Salzburg
🇦🇹Salzburg, Austria
Hanuschkrankenhaus Wien
🇦🇹Wien, Austria
Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Marienhospital Bochum-Herne
🇩🇪Bochum, Germany
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria