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

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™) in Adult Patients With Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia (CBF-AML)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02013648
• Other study ID #: AMLSG 21-13
• Status: Completed
• Phase: Phase 3
• Start date: July 2014
• Est. completion date: February 2024

Study information

• Verified date: February 2024
• Source: University of Ulm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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; in the investigational arm, consolidation therapy is followed by a one-year maintenance therapy with dasatinib. Patients with molecular disease persistence or molecular relapse as assessed by quantitative RQ-PCR for the CBF fusion transcripts will be eligible for hematopoietic stem cell transplantation before overt hematologic relapse occurs. Primary endpoint is event-free survival.

AML patients will be assessed for the CBF fusion genes in one of two AMLSG central laboratories within 48 hours of diagnosis, and only patients with CBF-AML will be enrolled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• 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;q22.1) (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.

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

• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dasatinib

• Cytarabine

• Daunorubicin

• Idarubicin

Locations

Country	Name	City	State
Austria	Universitätsklinik für Innere Medizin V	Innsbruck
Austria	Krankenhaus der Barmherzigen Schwestern	Linz
Austria	Krankenhaus der Elisabethinen Linz GmbH	Linz
Austria	Universitätsklinik der PMU	Salzburg
Austria	Hanuschkrankenhaus	Wien
Germany	Klinikum Aschaffenburg-Alzenau	Aschaffenburg
Germany	Helios Klinikum Bad Saarow, Klinik für Hämatologie	Bad Saarow
Germany	Charité Universitätsmedizin Campus Virchow Klinikum	Berlin
Germany	Klinikum am Urban	Berlin
Germany	Klinikum Neukölln	Berlin
Germany	Knappschaftskrankenhaus Bochum	Bochum
Germany	Universitätsklinikum Medizinische Klinik und Poliklinik III	Bonn
Germany	Städtisches Klinikum Braunschweig gGmbH	Braunschweig
Germany	Klinikum Bremen Mitte gGmbH	Bremen
Germany	Klinikum Darmstadt Medizinische Klinik V	Darmstadt
Germany	St. Johannes Hospital	Dortmund
Germany	Universitätsklinikum Medizinische Klinik und Poliklinik	Düsseldorf
Germany	Klinikum Esslingen	Esslingen
Germany	Malteser Krankenhaus St. Franziskus-Hospital	Flensburg
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	MVZ Osthessen	Fulda	Hessen
Germany	Wilhelm-Anton-Hospital gGmbH	Goch
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Klinikum Hanau GmbH	Hanau
Germany	Klinikum Region Hannover GmbH	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	SLK-Kliniken GmbH	Heilbronn
Germany	Marienhospital Klinikum der Ruhr-Universität	Herne
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Städtisches Klinikum Karlsruhe gGmbH	Karlsruhe
Germany	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein
Germany	Gemeinschaftspraxis Hämato-Onkologie	Lebach
Germany	Klinikum Lippe GmbH	Lemgo
Germany	Märkische Kliniken GmbH	Lüdenscheid
Germany	Univ-Klinikum der Otto-von Guericke-Universität	Magdeburg
Germany	III. Medizinische Klinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität	Mainz
Germany	Johannes Wesling Klinikum	Minden
Germany	Klinikum rechts der Isar der TU	München
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen
Germany	Ortenau Klinikum	Offenburg
Germany	Klinikum Oldenburg gGmbH	Oldenburg
Germany	PIUS Hospital	Oldenburg
Germany	Klinikum Passau	Passau
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Caritasklinkum Saarbrücken St. Theresia	Saarbrücken
Germany	Klinikum Stuttgart	Stuttgart
Germany	Vinzenz von Paul Kliniken gGmbH Marienhospital	Stuttgart
Germany	Klinikum Mutterhaus der Borromäerinnen gGmbH	Trier
Germany	Medizinische Universitätsklinik	Tübingen
Germany	Universitätsklinikum Ulm Zentrum für Innere Medizin	Ulm
Germany	Schwarzwald-Baar Klinikum	Villingen Schwenningen
Germany	Kliniken Essen Süd	Werden
Germany	HELIOS Klinikum	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	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	Cumulative incidence of relapse (CIR)		4 years
Secondary	Cumulative incidence of death (CID)		4 years
Secondary	overall survival		4 years
Secondary	relapse-free survival		4 years
Secondary	PIA analysis	Pharmacodynamic inhibition of KIT as assessed by the KIT plasma inhibitory assay (PIA)	4 years
Secondary	toxicity	Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03), timing and relatedness of non-hematologic toxicity observed during different treatment cycles.	7 months (standard arm) / 19 months (investigational arm)