Clinical Trials Register

Summary
EudraCT Number:	2011-006181-41
Sponsor's Protocol Code Number:	CA180399
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-12
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-006181-41

A.3

Full title of the trial

An open label, randomized (2:1) Phase 2b study of Dasatinib vs. Imatinib in patients with Chronic Phase Chronic Myeloid Leukemia who have not achieved an optimal response to 3 months of therapy with 400 mg Imatinib

A.3.1

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

Open label study with Dasatinib in patients with Chronic Phase Chronic Myeloid Leukemia treated with Imatinib

A.4.1

Sponsor's protocol code number

CA180399

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	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	EU Start Up Department
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance, Avenue de Finlande, 8
B.5.3.2	Town/ city	Braine l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.com

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 Pharma EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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.3.9.4	EV Substance Code	SUB23322
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	20 to 140
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Glivec
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/01/021
D.3 Description of the IMP
D.3.4	Pharmaceutical form	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	imatinib free base
D.3.9.1	CAS number	152459-95-5
D.3.9.3	Other descriptive name	IMATINIB
D.3.9.4	EV Substance Code	SUB25387
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	100 to 400
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

Chronic Phase Chronic Myeloid Leukemia

E.1.1.1

Medical condition in easily understood language

Chronic Phase Chronic Myeloid Leukemia

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10054352
E.1.2	Term	Chronic phase chronic myeloid leukemia
E.1.2	System Organ Class	100000013009

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the rate of major molecular response (MMR) at 12 months after Day 1 initiation of first line treatment with imatinib, in patients randomized at month 3 to treatment with dasatinib 100mg QD or imatinib at any dose, after less than optimal response to 1st line imatinib

E.2.2

Secondary objectives of the trial

To compare the following between both arms:
o time to MMR
o time to MR4.5
o Progression Free Survival (PFS)
o Overall Survival (OS)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. CML-CP patients with CHR but with BCR-ABL level > 10% IS after 3 months of imatinib 400 mg treatment. Imatinib monotherapy should have been started within 6 months of CP-CML diagnosis.
2. Men and women with CML-CP Ph+ > age 18
3. Currently tolerating imatinib 400 mg QD
4. ECOG performance status = 0 – 2
5. Patient willing and able to give informed consent
6. Life expectancy >6 months
7. Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN.
8. Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the institutional upper limit of normal (ULN).
9. Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal. Subjects with low K, Mg levels, total serum Ca and/or ionized Ca must be replete to allow for protocol entry.

E.4

Principal exclusion criteria

1. Patients who are pregnant or breastfeeding or likely to become pregnant.
2. Men whose partner is unwilling or unable to avoid pregnancy
3. Prior or concurrent malignancy, except for the following:
a. Curatively treated basal cell or squamous cell skin cancer
b. Cervical carcinoma in situ
c. Adequately treated Stage I or II cancer from which the subject is currently in complete remission
d. Any other cancer from which the subject has been disease free for 3 years
4. Documented T315I7A, F317L or V299L mutations (if already available – not required for screening)
5. Medical History and concurrent medical conditions, including:
a. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
b. Uncontrolled or significant cardiovascular disease, including any of the following:
i. Congestive cardiac failure (NYHA >2) within 3 months
ii. Diagnosed or suspected congenital long QT syndrome
iii. Any history of clinically significant ventricular arrhythmias
iv. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
v. Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
vi. Uncontrolled angina within 3 months
vii. Prior myocardial infarction within 6 months
viii. Uncontrolled hypertension
c. Pulmonary arterial hypertension
d. Pleural or pericardial effusions of any grade at randomisation are excluded. Subjects previously diagnosed with pleural/pericardial effusion of any grade resolved at the time of randomisation are allowed.
e. History of significant bleeding disorder unrelated to CML, including
i. Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)
ii. Diagnosed acquire bleeding disorder within on e year (e.g., acquired anti-factor VIII antibodies)
f. Prior chemotherapy for peripheral stem cell mobilization. (Prior collection of unmobilized peripheral blood stem cells is permitted).
g. Previous diagnosis of accelerated phase or blast crisis
h. Subjects with clonal evolution in Ph+ cells observed in ≥ 2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap tap at 3 months, are elegible for the study.
i. Subjects with less than Complete Hematologic Response (CHR) after 3 months of imatinib treatment or lost CHR after initial achievement.
j. Subjects intolerant to Imatinib 400 mg QD prior to enrolment.
l. Subjects with known hypersensitivity to excipients of dasatinib lactose monohydrate, microcrystalline cellulose, croscarmellose sodium; hydroxypropyl cellulose, magnesium stearate; Film 400).
6. Prohibited treatments and/or other treatments
a. History of TKI exposure within the previous 12 months apart from imatinib
b. Subject with any anti-CML other than imatinib (except HU or anagralide)
7. Subjects with prior stem cell transplantation and/or high dose chemotherapy for CML
8. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
Rescreening is permitted in the event of temporary biochemical abnormalities

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this study is the proportion of randomized subjects who achieve
MMR at 12 months after the first day (Day 1) treatment with first-line imatinib in
patients in each treatment group

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after day 1 imatinib treatment

E.5.2

Secondary end point(s)

Time to MMR, MR4.5, PFS, OS

E.5.2.1

Timepoint(s) of evaluation of this end point

at month 6, 12, 15, 18, 24, 36, 48, after day 1 of imatinib therapy

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)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Austria

Belgium

Brazil

Canada

China

Czech Republic

France

Italy

Korea, Republic of

Poland

Spain

Thailand

United States

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

Last patient, last visit

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

129

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

129

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

258

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the end of the study, BMS will not continue to supply study drug to
subjects/investigators. The investigator should ensure that the subject receives appropriate standard of care to treat the condition under study.
Subjects who have completed the trial and medically stable at study completion and without access to the drug (or are unable to receive reimbursement through other means) may be eligible to continue to receive the medication they were originally assigned in the trial.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-03-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-04-12

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