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

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ClinicalTrials.gov Identifier: NCT00850382

Recruitment Status : Completed

First Posted : February 25, 2009

Last Update Posted : March 1, 2016

Sponsor:

Information provided by (Responsible Party):

Prof. Dr. Hartmut Doehner, University of Ulm

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia (AML)	Drug: Dasatinib Drug: daunorubicin Drug: Cytarabine	Phase 1 Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	89 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Open-Label, Multicenter Phase Ib/IIa Study For the Evaluation of Dasatinib (Sprycel™) Following Induction and Consolida-tion Therapy as Well as in Maintenance Therapy in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)
Study Start Date :	June 2009
Actual Primary Completion Date :	November 2015
Actual Study Completion Date :	November 2015

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial acute myeloid leukemia with mutated CEBPA Cytogenetically normal acute myeloid leukemia Core binding factor acute myeloid leukemia

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Cytarabine Daunorubicin Dasatinib

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	Drug: 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). Drug: daunorubicin Induction cycle(s): Daunorubicin 60 mg/m2/day administered on days 1 through 3 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.

Arm

Intervention/treatment

Experimental: 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).

Drug: 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).

Drug: daunorubicin

Induction cycle(s):

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

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.

Outcome Measures

Primary Outcome Measures :

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 [ Time Frame: after 4 weeks ]

Secondary Outcome Measures :

Cumulative incidence of relapse (CIR) and death (CID) [ Time Frame: After follow-up period of two years ]
Overall survival (os) [ Time Frame: After follow-up period of two years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00850382

Locations

Show 50 study locations

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Austria
Universitätsklinikum Innsbruck
Innsbruck, Austria, 6020
Krankenhaus der Barmherzigen Schwestern
Linz, Austria, 4010
Elisabethinen Krankenhaus
Linz, Austria, 4020
Landeskliniken Salzburg
Salzburg, Austria, 5020
Hanuschkrankenhaus Wien
Wien, Austria, 1140
Germany
Ubbo-Emmius Klinik Aurich
Aurich, Germany, 26603
Charité Universitätsmedizin Berlin
Berlin, Germany, 13353
Universitätsklinikum Bonn
Bonn, Germany, 53105
Städtisches Klinikum Braunschweig
Braunschweig, Germany, 38114
Klinikum Bremen-Mitte gGmbH
Bremen, Germany, 28177
Klinikum Darmstadt
Darmstadt, Germany, 64283
Universitätsklinikum Duesseldorf
Duesseldorf, Germany, 40225
Kliniken Essen-Sued
Essen, Germany, 45239
Klinikum Esslingen
Esslingen, Germany, 73730
Städtische Kliniken Frankfurt Höchst
Frankfurt-Höchst, Germany, 65929
Medizinische Universitätsklinik
Freiburg, Germany, 79106
Medizinisches Versorgungszentrum Osthessen GmbH
Fulda, Germany, 36043
Klinik der Justus Liebig Universität
Gießen, Germany, 35385
Wilhelm- Anton- Hospital gGmbH
Goch, Germany, 47574
Universitätsmedizin Göttingen
Göttingen, Germany, 37075
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Asklepios Klinik Altona
Hamburg, Germany, 22763
Evangelisches Krankenhaus Hamm
Hamm, Germany, 59063
Klinikum Hanau gGmbH
Hanau, Germany, 63450
Klinikum Hannover Siloah
Hannover, Germany, 30449
Medizinische Hochschule Hannover
Hannover, Germany, 30625
SLK-Kliniken Heilbronn GmbH
Heilbronn, Germany, 74078
Universitätsklinikum des Saarlandes
Homburg Saar, Germany, 66424
Staedtisches Klinikum Karlsruhe
Karlsruhe, Germany, 76133
Staedtisches Krankenhaus Kiel GmbH
Kiel, Germany, 24116
Caritas Krankenhaus Lebach
Lebach, Germany, 66822
Klinikum Lippe-Lemgo
Lemgo, Germany, 32657
Klinikum Luedenscheid
Luedenscheid, Germany, 58515
Univ-Klinikum der Otto- von Guericke- Universität
Magdeburg, Germany, 39120
Universitätsklinikum der Johannes Gutenberguniversität Mainz
Mainz, Germany, 55131
Johannes Wesling Klinikum
Minden, Germany, 32429
Klinikum rechts der Isar der TU Muenchen
Muenchen, Germany, 81675
Klinikum Oldenburg
Oldenburg, Germany, 26133
Klinikum Passau
Passau, Germany, 94032
Elisabeth Krankenhaus
Recklinghausen, Germany, 45661
Krankenhaus der Barmherzigen Brueder
Regensburg, Germany, 93049
Caritas-Klinik St. Theresia
Saarbrücken, Germany, 66113
Klinikum Sindelfingen-Böblingen
Sindelfingen, Germany, 71065
Klinikum Stuttgart
Stuttgart, Germany, 70174
Diakonie-Klinikum Stuttgart
Stuttgart, Germany, 70176
Krankenhaus der Barmherzigen Brüder Trier
Trier, Germany, 54292
Medizinische Universitätsklinik Tuebingen
Tuebingen, Germany, 72076
Universitätsklinik Ulm
Ulm, Germany, 89081
Schwarzwald-Baar Klinikum
Villingen-Schwenningen, Germany, 78050
Helios Klinikum Wuppertal
Wuppertal, Germany, 42283

Sponsors and Collaborators

University of Ulm

Investigators

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Principal Investigator:	Hartmut Doehner, MD	University Hospital of Ulm

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Paschka P, Schlenk RF, Weber D, Benner A, Bullinger L, Heuser M, Gaidzik VI, Thol F, Agrawal M, Teleanu V, Lübbert M, Fiedler W, Radsak M, Krauter J, Horst HA, Greil R, Mayer K, Kündgen A, Martens U, Heil G, Salih HR, Hertenstein B, Schwänen C, Wulf G, Lange E, Pfreundschuh M, Ringhoffer M, Girschikofsky M, Heinicke T, Kraemer D, Göhring G, Ganser A, Döhner K, Döhner 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.

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Responsible Party:	Prof. Dr. Hartmut Doehner, Prof. Dr., University of Ulm
ClinicalTrials.gov Identifier:	NCT00850382
Other Study ID Numbers:	AMLSG 11-08
First Posted:	February 25, 2009 Key Record Dates
Last Update Posted:	March 1, 2016
Last Verified:	February 2016

Keywords provided by Prof. Dr. Hartmut Doehner, University of Ulm:


CBF AML Dasatinib Core Binding Factor (CBF)

Additional relevant MeSH terms:

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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms Cytarabine Daunorubicin Dasatinib Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action	Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Protein Kinase Inhibitors

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