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

NCT ID: NCT00850382

Last Updated: 2016-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2015-11-30

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib

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).

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: 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).

daunorubicin

Intervention Type: DRUG

Induction cycle(s):

Daunorubicin 60 mg/m2/day administered on days 1 through 3

Cytarabine

Intervention Type: 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.

Interventions

Dasatinib

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).

Intervention Type: DRUG

daunorubicin

Induction cycle(s):

Daunorubicin 60 mg/m2/day administered on days 1 through 3

Intervention Type: DRUG

Cytarabine

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Ulm

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Hartmut Doehner

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hartmut Doehner, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Ulm

Locations

Universitätsklinikum Innsbruck

Innsbruck, , Austria

Krankenhaus der Barmherzigen Schwestern

Linz, , Austria

Elisabethinen Krankenhaus

Linz, , Austria

Landeskliniken Salzburg

Salzburg, , Austria

Hanuschkrankenhaus Wien

Vienna, , Austria

Ubbo-Emmius Klinik Aurich

Aurich, , Germany

Charité Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Städtisches Klinikum Braunschweig

Braunschweig, , Germany

Klinikum Bremen-Mitte gGmbH

Bremen, , Germany

Klinikum Darmstadt

Darmstadt, , Germany

Universitätsklinikum Duesseldorf

Düsseldorf, , Germany

Kliniken Essen-Sued

Essen, , Germany

Klinikum Esslingen

Esslingen am Neckar, , Germany

Städtische Kliniken Frankfurt Höchst

Frankfurt-Höchst, , Germany

Medizinische Universitätsklinik

Freiburg im Breisgau, , Germany

Medizinisches Versorgungszentrum Osthessen GmbH

Fulda, , Germany

Klinik der Justus Liebig Universität

Giessen, , Germany

Wilhelm- Anton- Hospital gGmbH

Goch, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Asklepios Klinik Altona

Hamburg, , Germany

Evangelisches Krankenhaus Hamm

Hamm, , Germany

Klinikum Hanau gGmbH

Hanau, , Germany

Klinikum Hannover Siloah

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

SLK-Kliniken Heilbronn GmbH

Heilbronn, , Germany

Universitätsklinikum des Saarlandes

Homburg Saar, , Germany

Staedtisches Klinikum Karlsruhe

Karlsruhe, , Germany

Staedtisches Krankenhaus Kiel GmbH

Kiel, , Germany

Caritas Krankenhaus Lebach

Lebach, , Germany

Klinikum Lippe-Lemgo

Lemgo, , Germany

Klinikum Luedenscheid

Lüdenscheid, , Germany

Univ-Klinikum der Otto- von Guericke- Universität

Magdeburg, , Germany

Universitätsklinikum der Johannes Gutenberguniversität Mainz

Mainz, , Germany

Johannes Wesling Klinikum

Minden, , Germany

Klinikum rechts der Isar der TU Muenchen

München, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Klinikum Passau

Passau, , Germany

Elisabeth Krankenhaus

Recklinghausen, , Germany

Krankenhaus der Barmherzigen Brueder

Regensburg, , Germany

Caritas-Klinik St. Theresia

Saarbrücken, , Germany

Klinikum Sindelfingen-Böblingen

Sindelfingen, , Germany

Klinikum Stuttgart

Stuttgart, , Germany

Diakonie-Klinikum Stuttgart

Stuttgart, , Germany

Krankenhaus der Barmherzigen Brüder Trier

Trier, , Germany

Medizinische Universitätsklinik Tuebingen

Tübingen, , Germany

Universitätsklinik Ulm

Ulm, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

Helios Klinikum Wuppertal

Wuppertal, , Germany

Countries

Austria; Germany

References

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.

Reference Type: DERIVED

PMID: 29720733 (View on PubMed)

Other Identifiers

AMLSG 11-08

Identifier Type: -

Identifier Source: org_study_id