Clinical Trials Register

Summary
EudraCT Number:	2012-004259-36
Sponsor's Protocol Code Number:	DASAPOST
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-11-12
Trial 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

Spain - AEMPS

A.2

EudraCT number

2012-004259-36

A.3

Full title of the trial

Multicenter, open-label, non-randomized Phase II trial of dasatinib in patients with Chronic Myeloid Leukemia in Chronic Phase (CP-CML) who meet criteria for late suboptimal response after prior imatinib treatment.

Ensayo Clínico Fase II multicéntrico, abierto, no aleatorizado de dasatinib en pacientes con Leucemia Mieloide Crónica en Fase Crónica (LMC-FC) con criterios de respuesta subóptima tardía tras tratamiento con imatinib.

A.3.1

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

Phase II trial of dasatinib in patients with Chronic Myeloid Leukemia in Chronic Phase after prior imatinib treatment.

Ensayo Clínico de dasatinib en pacientes con Leucemia Mieloide Crónica en Fase Crónica tras tratamiento con imatinib.

A.3.2

Name or abbreviated title of the trial where available

DASAPOST

A.4.1

Sponsor's protocol code number

DASAPOST

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	Fundación PETHEMA
B.1.3.4	Country	Spain
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	Bristol-Myers Squibb S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dynamic
B.5.2	Functional name of contact point	Liana de Plasencia
B.5.3	Address:
B.5.3.1	Street Address	c/ Azcona, 31
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28028
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034914561105
B.5.5	Fax number	0034914561126
B.5.6	E-mail	l.plasencia@dynasolutions.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 20 mg comprimidos recubiertos
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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 Monohydrate
D.3.9.3	Other descriptive name	Dasatinib Monohydrate
D.3.9.4	EV Substance Code	SUB23159
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	20
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	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 50 mg comprimidos recubiertos
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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 monohydrate
D.3.9.3	Other descriptive name	Dasatinib monohydrate
D.3.9.4	EV Substance Code	SUB23159
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

Chronic Myeloid Leukemia in Chronic Phase

Leucemia Mieloide Crónica en Fase Crónica

E.1.1.1

Medical condition in easily understood language

Chronic Myeloid Leukemia

Leucemia Mieloide Crónica

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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	100000004864

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 assess the efficacy of dasatinib in terms of major molecular response rate at 6 months in patients with CP-CML who have achieved complete cytogenetic response without major molecular response after at least 18 months on Imatinib 400/600.

Evaluar la eficacia de dasatinib en términos de tasa de respuesta molecular mayor a 6 meses en pacientes con LMC-FC que han alcanzado una respuesta citogenética completa sin respuesta molecular mayor tras al menos 18 meses de tratamiento con Imatinib 400/600.

E.2.2

Secondary objectives of the trial

? To assess the efficacy of dasatinib in terms of depth and kinetics of molecular response.
? To assess the relationship of dasatinib with the appearance of large granular lymphocytes and assess the relationship of LGL with efficacy and toxicity.
? PFS

? Evaluar la eficacia de dasatinib en términos de profundidad y cinética de respuesta molecular.
? Evaluar la relación de dasatinib con la aparición de linfocitos. grandes granulares y evaluar la relación de LGL con la eficacia y toxicidad
? SLP

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Adult patients >or = 18 years
2 Diagnostic of Ph+ Chronic Myeloid Leukemia in first chronic phase
3 Treated with Imatinib 400 mg per day or 600 mg per day for at least 18 months. A wash out period of at least 7 days for imatinib is required prior to dasatinib administration
4 Patients meet criteria of late suboptimal response (complete cytogenetic response with no major molecular response) or have lost major molecular response
5 Ability to understand and voluntarily sign the informed consent form
6 Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy and have a negative pregnancy test, a maximum of 72 hours prior to study drug start. Sexually active men must also use effective contraceptive methods during the treatment.
7 Women must not be breastfeeding.

1 Pacientes adultos de > o = 18 años
2 Diagnóstico de Leucemia Mieloide Crónica Ph+ en primera Fase Crónica
3 Tratados con Imatinib 400 mg al día ó 600 mg al día durante al menos 18 meses.Se requiere un periodo de lavado de 7 días para el tratamiento previo con imatinib antes de iniciar el tratamiento con dasatinib
4 Pacientes que cumplan criterios de respuesta subóptima tardía (respuesta citogenética completa sin respuesta molecular mayor) o que hayan perdido la respuesta molecular mayor
5 Capacidad para entender y firmar voluntariamente el consentimiento informado
6 Las mujeres con capacidad fértil deben usar un método adecuado de contracepción para evitar el embarazo y deben tener un test de embarazo negativo, con un máximo de 72 horas antes de comenzar el tratamiento del estudio. Asimismo, los varones sexualmente activos deben utilizar métodos anticonceptivos eficaces durante el tratamiento.
7 Las mujeres no deben estar en periodo de lactancia materna

E.4

Principal exclusion criteria

1. Patients treated with Imatinib at a dose different of 400/600 mg per day

2. Patients treated with other TKI than imatinib

3. Loss of cytogenetic response at study entry

4. ECOG ? 3

5. Inadequate bone marrow reserve: ANC <1.5 x 109/L and/or Platelet count < 100 x 109/L

6. Inadequate hepatic function (Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)> 2.5 X institutional upper limit of normal (IULN). Total bilirubin > 1.5 X IULN (unless Gilbert syndrome has been diagnosed)

7. Inadequate renal function (serum Cr >3 UNL or ClCr <45 ml/min)

8. Patients receiving concurrent treatment with other experimental drugs or anti-cancer therapy

9. Patients with uncontrolled concurrent disease:
a) Known pleural effusion at baseline
b) Clinically-significant gastrointestinal disease or surgery that would compromise absorption of study drug (eg, uncontrolled nausea or malabsorption syndrome)
c) Clinically-significant known coagulation or platelet function disorder (not related to thrombocytopenia), eg, von Willebrand?s disease
d) Other active malignancy requiring concurrent intervention
e) Uncontrolled or significant cardiovascular disease, including any of the following:
- Myocardial infarction within 6 months of enrolment date
- Uncontrolled angina or congestive heart failure within 3 months of enrolment date
- Left ventricular ejection fraction (LVEF) < 40%
- Significant cardiac conduction abnormality, including history of clinically-significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe), history of third degree heart block or diagnosed congenital long QT syndrome, and/or prolonged QTc/f interval > 450 msec on baseline ECG.

10. Patients with active or uncontrolled infections or with serious illnesses or medical conditions that would not permit the patient to be managed according to the protocol.

11. Patients unable or unwilling to give written, informed consent prior to study participation.

1. Pacientes tratados con Imatinib a una dosis diferente a 400/600 mg al día

2. Pacientes tratados con otro inhibidor de tirosina kinasa distinto a imatinib

3. Pérdida de respuesta citogenética en el momento de la entrada en el estudio

4. ECOG ? 3

5. Reserva medular inadecuada: RAN <1.5 x 109/L y/o Plaquetas< 100 x 109/L

6. Función hepática inadecuada (Alanina aminotransferasa (ALT) y/o aspartato aminotransferasa (AST)> 2.5 X límite superior de la normalidad (LSN)). Bilirrubina Total > 1.5 X LSN (excepto si diagnóstico previo de sd. Gilbert)

7. Función renal inadecuada (Crs >3 UNL o ClCr <45 ml/min)

8. Pacientes en tratamiento concomitante con otros fármacos en investigación o tratamientos anti-cancer o fármacos de categoría I de riesgo de producir Torsades de Pointes (ver sección 3.4.1.2)

9. Pacientes con enfermedades concurrentes no controladas:
a) derrame pleural conocido en el momento basal
b) historia previa conocida de hipertensión pulmonar arterial
b) enfermedad o cirugía gastrointestinal clínicamente significativa que pudiera comprometer la absorción del fármaco del estudio (ej., náuseas no controladas o sd. de malabsorción)
c) alteración conocida de la coagulación o función plaquetaria clínicamente significativa (no relacionadas con trombopenia), ej, enfermedad de von Willebrand
d) otra enfermedad activa maligna que requiera intervención concomitante
e) enfermedad cardiovascular no controlada o significativa, incluyendo cualquiera de lo siguiente:
- Infarto de Miocardio dentro de los últimos 6 meses antes de la entrada en el estudio
- angina no controlada o Insuficiencia Cardiaca Congestiva dentro de los 3 meses previos a la entrada en el estudio
- fracción de eyección ventricular izquierda (LVEF) < 40%
-anomalía significativa de la conducción cardiaca, incluyendo historia de arritmia ventricular clínicamente relevante (como taquicardia ventricular, fibrilación ventricular o Torsades de Pointes), historia de bloqueo cardiaco de tercer grado o diagnóstico de sd. QT congénito, y/o intervalo QTc/f prolongado > 450 mseg respecto al ECG basal

10. Pacientes con infecciones activas o no controladas o con enfermedades médicas graves que no permitieran manejar al paciente de acuerdo con el protocolo

11. Pacientes que no desean dar su consentimiento informado por escrito a la entrada en el estudio

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the Major molecular response rate at 6 months of dasatinib treatment.

El objetivo primario de eficacia es la tasa de Respuesta Molecular Mayor tras 6 meses de tratamiento con dasatinib.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 6 months of dasatinib treatment.

Tras 6 meses de tratamiento con dasatinib.

E.5.2

Secondary end point(s)

The secondary efficacy endpoints include Major molecular response rate at 12 months, Complete molecular response rate at 6 and 12 moths, Incidence of lymphocytosis, Major and complete molecular response rates in patients with and without lymphocytosis and PFS.

Los objetivos secundarios de eficacia incluyen la tasa de Respuesta Molecular Mayor a 12 meses, la tasa de Respuesta Molecular Completa a 6 y 12 meses, la incidencia de linfocitosis, las tasas de Respuesta Molecular Mayor y Completa en pacientes con y sin linfocitosis y la SLP.

E.5.2.1

Timepoint(s) of evaluation of this end point

At 6 and 12 months of dasatinib treatment.

Tras 6 y 12 meses de tratamiento con dasatinib.

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

E.6.4

Safety

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

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

Yes

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

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

LVLS

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

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)

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

Information not present in EudraCT

F.3.3.7

Others

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

Standard clinical treatment

Práctica clínica habitual

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

2013-01-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-14

P. End of Trial
P.	End of Trial Status	Ongoing

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