Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™)

NCT02013648 | Completed Phase 3 DMC

• 1 other identifier: AMLSG 21-13
• Study Type: interventional
• Target: 204
• Locations: 2 countries
• Sites: 54

Brief Summary

This is a randomized phase III open-label, multicenter trial evaluating standard induction therapy (daunorubicin \[DNR\] and cytarabine \[Ara-C\]) and consolidation therapy (high-dose cytarabine \[HDAC\]) with or without dasatinib in adult patients with newly diagnosed CBF-AML

Conditions

Acute Myeloid Leukemia (AML)

Keywords

AML; Dasatinib; Core Binding Factor (CBF)

Outcome Measures

Primary Outcomes (1)

• Event-free Survival

  To assess event-free survival (EFS) after intensive induction (daunorubicin and cytarabine) and consolidation (high-dose cytarabine) chemotherapy with or without dasatinib in patients with CBF-AML

  4 years

Secondary Outcomes (6)

• Cumulative incidence of relapse (CIR)

  4 years

• Cumulative incidence of death (CID)

  4 years

• overall survival

  4 years

• relapse-free survival

  4 years

• PIA analysis

  4 years

Study Arms (2)

Standard arm

ACTIVE COMPARATOR

Patients will receive induction therapy with daunorubicin 60 mg/m2/day administered on days 1-3 (when daunorubicin is not available due to supply shortage: Idarubicin 12mg²/day on days 1,3,5) and cytarabine 200 mg/m2/day administered by continuous IV infusion on days 1-7. Patients achieving PR only at the end of cycle 1 will receive a second induction cycle with daunorubicin 50 mg/m2/day (when daunorubicin is not available due to supply shortage: Idarubicin 10 mg²/day on days 1 and 3) administered on days 1-3 and cytarabine 200 mg/m2/day administered by cont. IV infusion daily on days 1-5. Patients will receive 4 cycles of consolidation therapy. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, days 1-3 administered intravenously over three hours. Follow-up period: There is no maintenance therapy in the standard arm. Patients will be closely followed, in particular for molecular disease persistence or molecular relapse.

Drug: Cytarabine; Drug: Daunorubicin; Drug: Idarubicin

Investigational arm

EXPERIMENTAL

Patients will receive induction therapy with daunorubicin 60 mg/m2/day on days 1-3 (when daunorubicin is not available due to supply shortage: Idarubicin 12mg²/day on days 1,3,5) and cytarabine 200 mg/m2/day by cont. IV infusion on days 1-7. Patients will receive dasatinib 100 mg QD on days 8-21. Patients achieving PR only at the end of cycle 1 will receive a 2nd induction cycle with daunorubicin 50 mg/m2/day on days 1-3 (when daunorubicin is not available due to supply shortage: Idarubicin 10 mg²/day on days 1 and 3) and cytarabine 200 mg/m2/day by cont. IV infusion on days 1-5. Patients will receive dasatinib 100 mg QD on days 6-21. Consolidation therapy (4 cycles). Treatment consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, days 1-3 iv over 3 hours. Patients will receive dasatinib 100 mg QD on days 4-21. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).

Drug: Dasatinib; Drug: Cytarabine; Drug: Daunorubicin; Drug: Idarubicin

Interventions

Dasatinib DRUG

Also known as: Sprycel

Investigational arm

Cytarabine DRUG

Also known as: ARA-cell

Investigational arm; Standard arm

Daunorubicin DRUG

Also known as: Daunoblastin

Investigational arm; Standard arm

Idarubicin DRUG

Investigational arm; Standard arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Core-binding factor (CBF) AML with molecular diagnosis of RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22.1) (or a variant form) or of CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22)/t(16;16)(p13.1;q22) as assessed in one of the central AMLSG reference laboratories (Ulm, Hannover)
• Age ≥ 18; there is no upper age limit
• No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the diagnostic screening phase
• Non-pregnant and non-nursing. Due to the unknown teratogenic potential of dasatinib in humans, pregnant or nursing patients may not be enrolled. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL with-in 72 hours prior to registration. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control - one highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap) - AT THE SAME TIME, at least four weeks before she begins dasatinib therapy. "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.
• Men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking dasatinib and for 3 months after therapy is stopped, even if they have undergone a successful vasectomy.
• Signed written informed consent.

You may not qualify if:

• Performance status WHO \>2
• Pulmonary edema and/or pleural/pericardial effusion within 14 days of day 1. If edema/effusion resolves to CTC Grade ≤1, patients can be treated with dasatinib.
• Patients with ejection fraction \<50% by echocardiography within 14 days of day 1
• Organ insufficiency (creatinine \>1.5x upper normal serum level; bilirubin, AST or AP \>2.5x upper normal serum level; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)
• Uncontrolled infection
• 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.
• Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
• 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.

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (54)

Universitätsklinik für Innere Medizin V

Innsbruck, 6020, Austria

Location

Krankenhaus der Barmherzigen Schwestern

Linz, 4010, Austria

Location

Krankenhaus der Elisabethinen Linz GmbH

Linz, 4020, Austria

Location

Universitätsklinik der PMU

Salzburg, 5020, Austria

Location

Hanuschkrankenhaus

Vienna, 1140, Austria

Location

MVZ Osthessen

Fulda, Hesse, 36043, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Schleswig-Holstein, 24116, Germany

Location

Klinikum Aschaffenburg-Alzenau

Aschaffenburg, 63739, Germany

Location

Helios Klinikum Bad Saarow, Klinik für Hämatologie

Bad Saarow, 15526, Germany

Location

Klinikum am Urban

Berlin, 10967, Germany

Location

Klinikum Neukölln

Berlin, 12351, Germany

Location

Charité Universitätsmedizin Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Knappschaftskrankenhaus Bochum

Bochum, Germany

Location

Universitätsklinikum Medizinische Klinik und Poliklinik III

Bonn, 53105, Germany

Location

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, 38114, Germany

Location

Klinikum Bremen Mitte gGmbH

Bremen, 28117, Germany

Location

Klinikum Darmstadt Medizinische Klinik V

Darmstadt, 64276, Germany

Location

St. Johannes Hospital

Dortmund, 44137, Germany

Location

Universitätsklinikum Medizinische Klinik und Poliklinik

Düsseldorf, 40001, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Malteser Krankenhaus St. Franziskus-Hospital

Flensburg, 24939, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Wilhelm-Anton-Hospital gGmbH

Goch, 47574, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Klinikum Hanau GmbH

Hanau, 63450, Germany

Location

Klinikum Region Hannover GmbH

Hanover, 30449, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

SLK-Kliniken GmbH

Heilbronn, 74078, Germany

Location

Marienhospital Klinikum der Ruhr-Universität

Herne, 44625, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Städtisches Klinikum Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

Gemeinschaftspraxis Hämato-Onkologie

Lebach, 66822, Germany

Location

Klinikum Lippe GmbH

Lemgo, 32657, Germany

Location

Märkische Kliniken GmbH

Lüdenscheid, 58515, Germany

Location

Univ-Klinikum der Otto-von Guericke-Universität

Magdeburg, 39120, Germany

Location

III. Medizinische Klinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität

Mainz, 55131, Germany

Location

Johannes Wesling Klinikum

Minden, 32429, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Klinikum rechts der Isar der TU

München, 81675, Germany

Location

Ortenau Klinikum

Offenburg, 77654, Germany

Location

PIUS Hospital

Oldenburg, 26121, Germany

Location

Klinikum Oldenburg gGmbH

Oldenburg, 26133, Germany

Location

Klinikum Passau

Passau, 94032, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Caritasklinkum Saarbrücken St. Theresia

Saarbrücken, 66113, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

Vinzenz von Paul Kliniken gGmbH Marienhospital

Stuttgart, 70199, Germany

Location

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, 54290, Germany

Location

Medizinische Universitätsklinik

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm Zentrum für Innere Medizin

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, 78052, Germany

Location

Kliniken Essen Süd

Werden, 45239, Germany

Location

HELIOS Klinikum

Wuppertal, 42283, Germany

Location

Related Publications (2)

• Dohner H, Spath D, Saadati M, Fiedler W, Gotze KS, Koller E, Westermann J, Vogel W, Heuser M, Lubbert M, Tischler HJ, Germing U, Teichmann LL, Fransecky L, Wolfler A, Nachbaur D, Hertenstein B, Schroers R, Martens UM, von Harsdorf S, Radsak MP, Aschauer G, Weisshaar S, Corbacioglu A, Schrade A, Gaidzik VI, Thol FR, Paschka P, Bullinger L, Benner A, Dohner K, Ganser A. Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia. Blood. 2026 Jan 5:blood.2025030722. doi: 10.1182/blood.2025030722. Online ahead of print.

  PMID: 41490515 DERIVED

• Paschka P, Schlenk RF, Weber D, Benner A, Bullinger L, Heuser M, Gaidzik VI, Thol F, Agrawal M, Teleanu V, Lubbert M, Fiedler W, Radsak M, Krauter J, Horst HA, Greil R, Mayer K, Kundgen A, Martens U, Heil G, Salih HR, Hertenstein B, Schwanen C, Wulf G, Lange E, Pfreundschuh M, Ringhoffer M, Girschikofsky M, Heinicke T, Kraemer D, Gohring G, Ganser A, Dohner K, Dohner H. Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial. Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.

  PMID: 29720733 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Dasatinib; Cytarabine; Daunorubicin; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Hartmut Doehner, Prof. Dr.

  University of Ulm

  PRINCIPAL INVESTIGATOR

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: December 11, 2013
• First Posted: December 17, 2013
• Study Start: July 1, 2014
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: February 23, 2024

Record last verified: 2024-02

Locations

DE (49); AU (5)