Clinical Trials Register

Summary
EudraCT Number:	2008-008238-35
Sponsor's Protocol Code Number:	AMLSG11-08
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-03-23
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2008-008238-35

A.3

Full title of the trial

Open-Label, Multicenter Phase II Study For the Evaluation of Dasatinib (Sprycel™) Following Induction and Consolidation Therapy as well as in Maintenance Therapy in Patients With Newly Diagnosed Core-Binding Factor (CBF) Acute Myeloid Leukemia (AML)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Offene, multizentrische Phase II-Studie zu Dasatinib (Sprycel™) im Anschluss an die Induktions- und Konsolidierungstherapie sowie als Erhaltungstherapie bei Patienten mit neu diagnostizierter Core-Binding-factor (CBF) akuter myeloischer Leukämie (AML)

A.3.2

Name or abbreviated title of the trial where available

AMLSG 11-08

A.4.1

Sponsor's protocol code number

AMLSG11-08

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00850382

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Universitätsklinikum Ulm
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Universitätsklinikum Ulm
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Bristol Myers Squibb
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitätsklinikum Ulm
B.5.2	Functional name of contact point	AMLSG Studienzentrale
B.5.3	Address:
B.5.3.1	Street Address	Albert-Einstein-Allee 23
B.5.3.2	Town/ city	Ulm
B.5.3.3	Post code	89081
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49731500 45900
B.5.5	Fax number	+49731500 45905
B.5.6	E-mail	richard.schlenk@uniklinik-ulm.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Sprycel®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol Myers Squibb
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sprycel®
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dasatinib
D.3.9.1	CAS number	302962-49-8
D.3.9.2	Current sponsor code	BMS-354825
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Newly diagnosed core binding factor acute myeloid leukemia.

E.1.1.1

Medical condition in easily understood language

Newly diagnosed core binding factor acute myeloid leukemia

neu diagonstizierte Core-Binding-factor (CBF) AML

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary Objective:
To assess relapse-free survival (RFS) after intensive induction (daunorubicin and cytara-bine) and consolidation (high-dose cytarabine) chemotherapy given in combination with dasatinib followed by a one-year single agent dasatinib maintenance therapy

E.2.2

Secondary objectives of the trial

Secondary Objective(s):
• To assess cumulative incidence of relapse (CIR) and death (CID)
• To assess overall survival (OS)
• To assess toxicity
• To assess the predictive value of KIT mutation / KIT expression
• To assess pharmacodynamic inhibition of KIT

E.2.3

Trial contains a sub-study

E.3

Principal 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

E.4

Principal 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 can-cers. 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 re-lapse within one year.
• 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 as well as information of the family physician about study participation.

E.5 End points

E.5.1

Primary end point(s)

• Relapse-free survival (RFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint feasibility is monitored throughout the trial. Sequential tests will be performed after each new primary event during induction, consolidation and maintenance therapy, in order to determine whether the tolerated rate of any of the event rates is exceeded.

E.5.2

Secondary end point(s)

Secondary endpoints:
• Cumulative incidence of relapse (CIR) and death CID)
• Overall survival (OS)
• RFS and OS of patients with mutated and wildtype KIT
• KIT phosphorylation as assessed by the KIT plasma inhibitory assay (PIA)

Safety endpoints:
• Rate of early deaths and hypoplastic deaths (ED/HD)
• Type, frequency, severity (graded using the National Cancer Institute Common Termi-nology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of non-hematological toxicity observed during different treatment cycles
• Duration of leuko-, neutro-, and thrombocytopenia after induction and consolidation ther-apy

E.5.2.1

Timepoint(s) of evaluation of this end point

at the end of study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase II

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

-> provided in the protocol chapter 19 "SPONSOR DISCONTINUATION CRITERIA"

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1