Dasatinib (Sprycel™) in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

NCT00850382 | Completed Phase 1

• 1 other identifier: AMLSG 11-08
• Study Type: interventional
• Target: 89
• Locations: 2 countries
• Sites: 50

Brief Summary

This is a Phase Ib/IIa open-labeled multi-center trial evaluating the feasibility of dasatinib given after standard induction therapy with daunorubicin (DNR) and cytarabine (ARA-C), after consolidation therapy with high-dose cytarabine (HDAC), and as single agent in a one-year maintenance therapy in patients with newly diagnosed CBF AML. 82 patients with newly diagnosed CBF AML will be enrolled at AMLSG study centers. All AML patients will be assessed for the CBF fusion genes via the central laboratory of the AMLSG within 48 hours of diagnosis of AML, and only patients with CBF AML will be enrolled into the study.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

CBF AML; Dasatinib; Core Binding Factor (CBF)

Outcome Measures

Primary Outcomes (1)

• Feasibility as combined endpoint: Rate of ED/HD Rate of pleural/pericardial effusion grade 3/4 Rate of liver toxicity grade 3/4 that does not improve to <= grade 2 within 14 days after discontinuing responsible medication Rate of refractory disease

  after 4 weeks

Secondary Outcomes (2)

• Cumulative incidence of relapse (CIR) and death (CID)

  After follow-up period of two years

• Overall survival (os)

  After follow-up period of two years

Study Arms (1)

Dasatinib

EXPERIMENTAL

Induction cycle(s): Patients will receive in cycle 1 induction therapy with daunorubicin 60 mg/m2/day administered on days 1 through 3 and cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Patients will receive dasatinib 100 mg QD on days 8-21. Patients not achieving CR or CRi at the end of cycle 1 will be evaluable to receive a second induction cycle identical in schedule and dosage to the first induction cycle. Consolidation Cycles 1, 2, 3, 4: Patients achieving CR or CRi at the end of cycle 1 will receive consolidation therapy for 4 cy-cles. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours. Patients will receive dasatinib 100 mg QD on days 6-28. 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: daunorubicin; Drug: Cytarabine

Interventions

Dasatinib DRUG

Induction cycle(s): Dasatinib 100 mg QD on days 8-21. Consolidation Cycles 1, 2, 3, 4: Patients will receive dasatinib 100 mg QD on days 6-28. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).

Dasatinib

daunorubicin DRUG

Induction cycle(s): Daunorubicin 60 mg/m2/day administered on days 1 through 3

Dasatinib

Cytarabine DRUG

Induction cycle(s): Cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Consolidation cycles 1, 2, 3, 4: Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours.

Dasatinib

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) (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.
• Age ≥ 18; there is no upper age limit.
• No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the diag-nostic 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 poten-tial (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 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 con-tact with women of childbearing potential while taking dasatinib and for 4 weeks 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
• Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
• Known positive for HIV
• Bleeding disorder independent of leukemia
• No consent for registration, storage and processing of the individual disease-characteristics and course

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (50)

Universitätsklinikum Innsbruck

Innsbruck, 6020, Austria

Location

Krankenhaus der Barmherzigen Schwestern

Linz, 4010, Austria

Location

Elisabethinen Krankenhaus

Linz, 4020, Austria

Location

Landeskliniken Salzburg

Salzburg, 5020, Austria

Location

Hanuschkrankenhaus Wien

Vienna, 1140, Austria

Location

Ubbo-Emmius Klinik Aurich

Aurich, 26603, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Städtisches Klinikum Braunschweig

Braunschweig, 38114, Germany

Location

Klinikum Bremen-Mitte gGmbH

Bremen, 28177, Germany

Location

Klinikum Darmstadt

Darmstadt, 64283, Germany

Location

Universitätsklinikum Duesseldorf

Düsseldorf, 40225, Germany

Location

Kliniken Essen-Sued

Essen, 45239, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Städtische Kliniken Frankfurt Höchst

Frankfurt-Höchst, 65929, Germany

Location

Medizinische Universitätsklinik

Freiburg im Breisgau, 79106, Germany

Location

Medizinisches Versorgungszentrum Osthessen GmbH

Fulda, 36043, Germany

Location

Klinik der Justus Liebig Universität

Giessen, 35385, Germany

Location

Wilhelm- Anton- Hospital gGmbH

Goch, 47574, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, 59063, Germany

Location

Klinikum Hanau gGmbH

Hanau, 63450, Germany

Location

Klinikum Hannover Siloah

Hanover, 30449, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, 74078, Germany

Location

Universitätsklinikum des Saarlandes

Homburg Saar, 66424, Germany

Location

Staedtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

Staedtisches Krankenhaus Kiel GmbH

Kiel, 24116, Germany

Location

Caritas Krankenhaus Lebach

Lebach, 66822, Germany

Location

Klinikum Lippe-Lemgo

Lemgo, 32657, Germany

Location

Klinikum Luedenscheid

Lüdenscheid, 58515, Germany

Location

Univ-Klinikum der Otto- von Guericke- Universität

Magdeburg, 39120, Germany

Location

Universitätsklinikum der Johannes Gutenberguniversität Mainz

Mainz, 55131, Germany

Location

Johannes Wesling Klinikum

Minden, 32429, Germany

Location

Klinikum rechts der Isar der TU Muenchen

München, 81675, Germany

Location

Klinikum Oldenburg

Oldenburg, 26133, Germany

Location

Klinikum Passau

Passau, 94032, Germany

Location

Elisabeth Krankenhaus

Recklinghausen, 45661, Germany

Location

Krankenhaus der Barmherzigen Brueder

Regensburg, 93049, Germany

Location

Caritas-Klinik St. Theresia

Saarbrücken, 66113, Germany

Location

Klinikum Sindelfingen-Böblingen

Sindelfingen, 71065, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

Diakonie-Klinikum Stuttgart

Stuttgart, 70176, Germany

Location

Krankenhaus der Barmherzigen Brüder Trier

Trier, 54292, Germany

Location

Medizinische Universitätsklinik Tuebingen

Tübingen, 72076, Germany

Location

Universitätsklinik Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, 78050, Germany

Location

Helios Klinikum Wuppertal

Wuppertal, 42283, Germany

Location

Related Publications (1)

• 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; Daunorubicin; Cytarabine

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; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Hartmut Doehner, MD

  University Hospital of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: February 23, 2009
• First Posted: February 25, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 1, 2016

Record last verified: 2016-02

Locations

AU (5); DE (45)