AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT01477606

Protocol in Acute Myeloid Leukemia With FLT3-ITD

A Phase 2 study testing Midostaurin, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by University of Ulm at 55 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Midostaurin, Cytarabine and Daunorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
451 participants
Where
55 sitesin 2 countries
Study dates
May 2012to 26 Feb 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 11Show fewer
  • 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.

Who cannot join

  • •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
Show all 11Show fewer
  • 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.

Trial locations and contacts

55 sites in 2 countries.

55 sites in 2 countries

Germany50 sites

  • Helios Klinikum Bad Saarow

    Bad Saarow, 15526

  • Vivantes Klinikum Neukölln

    Berlin, 12351

  • Charité Universitätsmedizin Berlin

    Berlin, 13353

  • Marienhospital Bochum-Herne

    Bochum, 44625

  • Medizinische Universitätsklinik Bochum

    Bochum, 44892

  • Universitätsklinikum Bonn

    Bonn, 53105

  • Städtisches Klinikum Braunschweig gGmbH

    Braunschweig, 38114

  • Klinikum Bremen-Mitte gGmbH

    Bremen, 64276

  • Klinikum Darmstadt

    Darmstadt, 64276

  • Universitätsklinkum Düsseldorf

    Düsseldorf, 40225

  • Kliniken Essen-Süd

    Essen, 45239

  • Klinik für Onkologie, Gastroenterologie und Allg. Innere Medizin Esslingen

    Esslingen am Neckar, 73730

  • Malteser Krankenhaus St. Franziskus Hospital Flensburg

    Flensburg, 24939

  • Medizinische Universitätsklinik Freiburg

    Freiburg im Breisgau, 79106

  • MVZ Osthessen

    Fulda, 36043

  • Klinik der Justus-Liebig-Universität Gießen

    Giessen, 35385

  • Wilhelm-Anton-Hospital gGmbH Goch

    Goch, 47574

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Universitätsklinikum Eppendorf

    Hamburg, 20246

  • Asklepios Klinik Altona

    Hamburg, 22763

  • Evangelisches Krankenhaus Hamm

    Hamm, 59063

  • Klinikum Region Hannover GmbH

    Hanover, 30449

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • SLK Kliniken Heilbronn GmbH

    Heilbronn, 74078

  • Universitätskliniken des Saarlandes

    Homburg/Saar, 66421

  • Städtisches Klinikum Karlsruhe

    Karlsruhe, 76133

  • Städtisches Krankenhaus Kiel GmbH

    Kiel, 24116

  • Caritas Krankenhaus Lebach

    Lebach, 66822

  • Klinikum Lippe-Lemgo

    Lemgo, 32657

  • Märkische Kliniken GmbH Lüdenscheid

    Lüdenscheid, 58515

  • Universitätsklinikum der Otto-von-Guericke Universität Magdeburg

    Magdeburg, 39120

  • Universitätsklinikum der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

  • Johannes Wesling Klinikum Minden

    Minden, 32429

  • Klinikum Schwabing

    München, 80804

  • Klinikum rechts der Isar der TU München

    München, 81675

  • Stauferklinikum Mutlangen

    Mutlangen, 73557

  • Ortenau Klinikum

    Offenburg, 77654

  • Pius Hospital Oldenburg

    Oldenburg, 26121

  • Klinikum Oldenburg

    Oldenburg, 26133

  • Klinikum Passau

    Passau, 94032

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Caritasklinik St. Theresia Saarbrücken

    Saarbrücken, 66113

  • Klinikum Stuttgart

    Stuttgart, 70174

  • Diakonie-Klinikum Stuttgart

    Stuttgart, 70176

  • Klinikum Mutterhaus der Borromäerinnen gGmbH Trier

    Trier, 54290

  • Krankenhaus der Barmherzigen Brüder Trier

    Trier, 54292

  • Medizinische Universitätsklinik Tübingen

    Tübingen, 72076

  • University Hospital of Ulm

    Ulm, 89081

  • Schwarzwald-Baar Klinikum Villingen-Schwenningen

    Villingen-Schwenningen, 78050

  • Helios Klinikum Wuppertal

    Wuppertal, 42283

Other trials in Germany

Austria5 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 3020

  • Krankenhaus der Barmherzigen Schwestern Linz

    Linz, 4010

  • Krankenhaus der Elisabethinen Linz GmbH

    Linz, 4020

  • Universitätsklinik für Innere Medizin III Salzburg

    Salzburg, 5020

  • Hanuschkrankenhaus Wien

    Vienna, 1140

Other trials in Austria

About this study

Official title: Phase-II Study Evaluating Midostaurin in Induction, Consolidation and Maintenance Therapy Also After Allogeneic Blood Stem Cell Transplantation in Patients With Newly Diagnosed Acute Myeloid Leukemia Exhibiting a FLT3 Internal Tandem Duplication

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.

Read more

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

Being tested
Midostaurin, Cytarabine, Daunorubicin
Keywords
Acute myeloid leukemia, FLT3-ITD, midostaurin (PKC412)
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MidostaurinDrug

    Also called PKC412

    Induction therapy: 50 mg, oral, twice daily, starting on day 8, thereafter continuous dosing until 48h before start of subsequent chemotherapy cycle.

    Consolidation therapy: 50 mg, oral twice daily, starting on day 6, thereafter continuous dosing until 48h before start of conditioning therapy for allogeneic HSCT or 48h before start of subsequent consolidation chemotherapy.

    Maintenance therapy:

    50 mg oral twice daily over one year.

  • CytarabineDrug

    Induction therapy:

    200 mg/m2/day by continuous i.v. infusion on days 1-7 (total dose 1400 mg/m²)

    Consolidation therapy:

    Younger adult patients (18 to 65 yrs): 3 g/m2 by i.v infusion over 3 hours every 12 hours on days 1, 3, and 5 (total dose 18 g/m2).

    Older patients (>65 yrs): 1 g/m2 by i.v. infusion over 3 hours every 12 hours on days 1, 3, and 5 (total dose 6 g/m2).

  • DaunorubicinDrug

    Induction therapy:

    60 mg/m², by 1-hour i.v. infusion, day 1-3 (total dose 180 mg/m²)

Study groups in NCT01477606
Study groupRoleWhat they receive
MidostaurinExperimentalNot described
Receives: Drug: Midostaurin; Drug: Cytarabine; Drug: Daunorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival

    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.

    Measured: 8years

Secondary outcomes (11)

  1. Rate of complete remission (CR)

    Measured: Two months

  2. Relapse-free survival

    Measured: 8 years

  3. overall survival

    Measured: 8 years

  4. Cumulative incidence of relapse

    Measured: 8 years

  5. cumulative incidence of death in CR

    Measured: 8 years

  6. Target (FLT3) inhibition by measuring the FLT3 plasma inhibitory activity

    Evaluation of target (FLT3) inhibition by continuous dosing of midostaurin

    Measured: 8 years

  7. Quality of life

    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.

    Measured: 5 years

  8. Rate of early deaths and hypoplastic deaths (ED/HD)

    Measured: two months

  9. Death in CR

    Measured: 8 years

  10. Toxicities

    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

    Measured: between 18 and 24 months

  11. Impact of allogeneic HSCT

    Assessment of the relative impact of allogeneic HSCT analyzed as time-dependent variable on survival endpoints.

    Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2011 (estimated)
  2. Study startMay 2012
  3. Primary completion26 Feb 2020
  4. Study completion26 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
451 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01477606
Sponsor's protocol ID
AMLSG 16-10
Other IDs
2011-003168-63
Status last verified
Jun 2020
First submitted
17 Nov 2011
Last updated
4 Jun 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Dohner H, Weber D, Krzykalla J, Fiedler W, Wulf G, Salih H, Lubbert M, Kuhn MWM, Schroeder T, Salwender H, Gotze K, Westermann J, Fransecky L, Mayer K, Hertenstein B, Ringhoffer M, Tischler HJ, Machherndl-Spandl S, Schrade A, Paschka P, Gaidzik VI, Theis F, Thol F, Heuser M, Schlenk RF, Bullinger L, Saadati M, Benner A, Larson R, Stone R, Dohner K, Ganser A. Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications. Blood Adv. 2022 Sep 27;6(18):5345-5355. doi: 10.1182/bloodadvances.2022007223.

    PubMed 35486475

  • Schlenk RF, Weber D, Fiedler W, Salih HR, Wulf G, Salwender H, Schroeder T, Kindler T, Lubbert M, Wolf D, Westermann J, Kraemer D, Gotze KS, Horst HA, Krauter J, Girschikofsky M, Ringhoffer M, Sudhoff T, Held G, Derigs HG, Schroers R, Greil R, Griesshammer M, Lange E, Burchardt A, Martens U, Hertenstein B, Marretta L, Heuser M, Thol F, Gaidzik VI, Herr W, Krzykalla J, Benner A, Dohner K, Ganser A, Paschka P, Dohner H; German-Austrian AML Study Group. Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood. 2019 Feb 21;133(8):840-851. doi: 10.1182/blood-2018-08-869453. Epub 2018 Dec 18.

    PubMed 30563875

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Midostaurin, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by University of Ulm at 55 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (time frame: 8years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01477606, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in