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

Acute Myeloid Leukemia (AML) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00850382
• Other study ID #: AMLSG 11-08
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 23, 2009
• Last updated: February 29, 2016
• Start date: June 2009
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: University of Ulm
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
Austria	Universitätsklinikum Innsbruck	Innsbruck
Austria	Elisabethinen Krankenhaus	Linz
Austria	Krankenhaus der Barmherzigen Schwestern	Linz
Austria	Landeskliniken Salzburg	Salzburg
Austria	Hanuschkrankenhaus Wien	Wien
Germany	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	Duesseldorf
Germany	Kliniken Essen-Sued	Essen
Germany	Klinikum Esslingen	Esslingen
Germany	Städtische Kliniken Frankfurt Höchst	Frankfurt-Höchst
Germany	Medizinische Universitätsklinik	Freiburg
Germany	Medizinisches Versorgungszentrum Osthessen GmbH	Fulda
Germany	Klinik der Justus Liebig Universität	Gießen
Germany	Wilhelm- Anton- Hospital gGmbH	Goch
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Asklepios Klinik Altona	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Evangelisches Krankenhaus Hamm	Hamm
Germany	Klinikum Hanau gGmbH	Hanau
Germany	Klinikum Hannover Siloah	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
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	Luedenscheid
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	Muenchen
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	Diakonie-Klinikum Stuttgart	Stuttgart
Germany	Klinikum Stuttgart	Stuttgart
Germany	Krankenhaus der Barmherzigen Brüder Trier	Trier
Germany	Medizinische Universitätsklinik Tuebingen	Tuebingen
Germany	Universitätsklinik Ulm	Ulm
Germany	Schwarzwald-Baar Klinikum	Villingen-Schwenningen
Germany	Helios Klinikum Wuppertal	Wuppertal

Sponsors (1)

Lead Sponsor	Collaborator
University of Ulm

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Cumulative incidence of relapse (CIR) and death (CID)		After follow-up period of two years	Yes
Secondary	Overall survival (os)		After follow-up period of two years	No