Clinical Trials Register

Summary
EudraCT Number:	2013-004323-37
Sponsor's Protocol Code Number:	BOS-IIG-01
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:	2015-02-09
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2013-004323-37

A.3

Full title of the trial

Single nucleotide polymorphism association with response and toxic effects in patients with Ph+ CP-CML treated with bosutinib after relapse or intolerance to previous treatment.

Estudio de correlación de polimorfismos con la respuesta y toxicidad a bosutinib en pacientes con Leucemia Mieloide Crónica (LMC) cromosoma Filadelfia positivo en fase crónica con respuesta no óptima a tratamiento previo

A.3.1

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

Single nucleotide polymorphism association with response and toxic effects in patients with Ph+ CP-CML treated with bosutinib after relapse or intolerance to previous treatment.

A.3.2

Name or abbreviated title of the trial where available

BOSTRO

A.4.1

Sponsor's protocol code number

BOS-IIG-01

A.5.4

Other Identifiers

Name:

GELMC-BOS-2013-02

Number:

GELMC-BOS-2013-02

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 para el tratamiento de la leucemia y el linfoma
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	Pfizer, S.L.U.
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	Fundación Pethema
B.5.2	Functional name of contact point	Dr. Alfonso J. Santiago Marí
B.5.3	Address:
B.5.3.1	Street Address	Hospital Clínico San Carlos. Calle Profesor Martín Lagos, s/n
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28040
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34609282632
B.5.5	Fax number	+34913303321
B.5.6	E-mail	alfonso.santiago@pethema.es

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	No
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	Bosutinib
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	BOSUTINIB
D.3.9.1	CAS number	380843-75-4
D.3.9.4	EV Substance Code	SUB29176
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	100
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

Patients with chromosome Philadelphia positive (Ph+) in chronic phase mielogenus leukemia (CP CML)

Leucemia mieloide Crónica cromosoma Filadelfia positivo en fase crónica con respuesta no óptima a tratamiento previo

E.1.1.1

Medical condition in easily understood language

Patients with chromosome Philadelphia positive (Ph+) in chronic phase mielogenus leukemia (CP CML)

Leucemia mieloide Crónica cromosoma Filadelfia positivo en fase crónica con respuesta no óptima a tratamiento previo

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10034877
E.1.2	Term	Philadelphia chromosome positive
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess single nucleotide polymorphisms in genes potentially relevant for bosutinib action, metabolism and transport and if there is an association between this and the drug activity and toxicity.

Determinar si polimorfismos de nucleótido único en genes potencialmente relevantes para el metabolismo, transporte y actividad de bosutinib se asocian con diferencias en respuesta y en toxicidad del fármaco.

E.2.2

Secondary objectives of the trial

- Assess the eficacy and toxicity of bosutinib in patients after relapse or intolerance to previous tyrosine kinase inhibitors .
- Assess the bosutinib eficacy reason depending on the failure of the previous treatment.

?Evaluar la eficacia y toxicidad del tratamiento con bosutinib en pacientes con respuesta no óptima a los 3 meses con otros inhibidores de tirosina kinasa.
?Analizar la eficacia de bosutinib de acuerdo a las causas por las que se alcanzó una respuesta no óptima al tratamiento previo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Signed and dated informed consent form.
2.Patients with chronic phase of Ph+ CML who showed failure to previous TKI treatment. Failure is defined as BCR-ABL >10% by qRT-PCR (IS) at 3 months of treatment initiation.
3.ECOG Performance Status of 0 or 1.
4.Recovered to Grade 0-1, or to baseline, from any toxicities of prior treatment, other than alopecia
5.Able to take daily oral capsules
6.Adequate bone marrow function: a. Absolute neutrophil count > 1000/mm3 (>1000 x109/L) b. Platelets ? 100,000/mm3 (>100 x109/L) absent any platelet transfusions during the preceding 14 days.
7.Adequate hepatic, and renal function:
oAST/ALT ? 2.5 × upper limit of normal (ULN) or ? 5 × ULN if attributable to liver involvement of leukemia
oTotal bilirubin ? 1.5 × ULN
oCreatinine ? 1.5 × ULN
8.Age > 18 years
9.Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of Bosutinib.

1.Consentimiento informado firmado y fechado.
2.Pacientes con LMC Ph+ en fase crónica que hayan presentado respuesta no óptima a los 3 meses a tratamiento previo ITK (imatinib, nilotinib, dasatinib). Se define como respuesta no optima BCR-ABL >10% por qRT-PCR (IS) a los 3 meses de inicio del tratamiento.
3.Estado funcional ECOG de 0 o 1.
4.Recuperación a Grado 0-1, o con el valor basal de cualquier toxicidad del tratamiento previo, excepto alopecia.
5.Capacidad para tomar cápsulas orales diariamente.
6.Adecuada función de la médula ósea:
?Recuento absoluto de neutrófilos > 1.000/mm3 (>1.000 x109/L)
?Plaquetas ? 100.000/mm3 (>100 x109/L)
?Ausencia de transfusión de plaquetas durante los 14 días precedentes.
7.Función hepática y renal adecuadas:
?AST/ALT ?2.5 × límite superior de normalidad (LSN). (Si la elevación se considera secundaria al tratamiento previo se podrá realizar una segunda determinación que demuestre la desaparición de esta toxicidad)
?Bilirrubina total ?1.5 × LSN.
?Creatinina ?1.5 × LSN.
8.Edad > 18 años.
9.La voluntad de los sujetos de ambos sexos, que no hayan sido esterilizados quirúrgicamente o estén en la postmenopausia, de usar métodos anticonceptivos fiables (anticonceptivos orales, dispositivos intrauterinos o métodos de barrera que utilizan espermicida) durante la duración del estudio y durante 30 días después de la última dosis de bosutinib.

E.4

Principal exclusion criteria

1.Subjects with Philadelphia chromosome and bcr-abl negative CML.
2. Overt leptomeningeal leukemia. Subjects must be free of CNS involvement for a minimum of 2 months. Subjects with symptoms of CNS involvement must have a diagnostic lumbar puncture prior to study enrollment.
3.Subjects with extramedullary disease only.
4.Prior stem cell transplantation.
5.Major surgery within 14 days or radiotherapy within 7 days before the first dose of Bosutinib (recovery from any previous surgery should be complete before day 1)
6.A history of a clinically significant ventricular arrhythmia, congenital or acquired prolonged QT interval, a baseline QTcF > 0.47 sec (average of triplicate readings) or unexplained syncope, uncontrolled or symptomatic congestive heart failure (CHF) within 3 months, or myocardial infarction (MI) within 6 months.
7.Concomitant use of or need for medications known to prolong the QT interval
8.Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval
9.Recent (within 30 days of study entry) or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, short bowel syndrome, bleeding, or grade >1 diarrhea, nausea or emesis lasting more than 2 days, despite adequate medical therapy)
10.Pregnant or breastfeeding women
11.Evidence of serious active infection, or significant medical or psychiatric illness
12.Known seropositivity to HIV, or current acute or chronic Hepatitis B or Hepatitis C (antigen positive), cirrhosis, hypokalemia (any grade), or clinically significant abnormal laboratory finding that would, in the investigator?s judgment, make the subject inappropriate for this study.

1.Sujetos con LMC cromosoma Filadelfia y bcr-abl negativa.
2.Leucemia leptomeníngea conocida. Los sujetos deben estar libres de afectación del SNC durante un mínimo de 2 meses. Los sujetos con síntomas de afectación del SNC deben tener una punción lumbar diagnóstica antes de entrar en el estudio.
3.Sujetos con una enfermedad exclusivamente extramedular.
4.Trasplante previo de células madre.
5.Cirugía mayor antes de 14 días o radioterapia 7 días antes de la primera dosis de bosutinib (la recuperación de cualquier cirugía previa debe ser completa antes del día 1).
6.Historia de arritmia ventricular clínicamente significativa, prolongación del intervalo QT congénita o adquirida, una situación basal de QTcF> 0,47 seg (promedio de las lecturas por triplicado) o síncope inexplicable, insuficiencia cardiaca congestiva sintomática (ICC) no controlada en los 3 meses previos, o infarto de miocardio (IM ) dentro de los 6 meses.
7.Uso o necesidad de medicamentos que se sepa que prolongan el intevalo QT.
8.Hipomagnesemia o hipopotasemia no corregida debida a los posibles efectos sobre el intervalo QT.
9.Alteración gastrointestinal reciente (dentro de 30 días del inicio del estudio) o actual (p.e., malabsorción, síndrome del intestino corto, sangrado, diarrea de grado >1, náusea o émesis de más de dos días de duración, a pesar de adecuada terapia médica.
10.Mujeres embarazadas o en lactancia.
11.Evidencia de infección activa seria, o enfermedad médica o psiquátrica importante.
12.Seropositividad para el VIH (Virus de la Inmunodeficiencia Humana), o hepatitis B o C (antígeno positiva) aguda o crónica actuales, cirrosis, hipopotasemia (cualquier grado), o cualquier hallazgo de laboratorio clínicamente significativo que pueda, a juicio del investigador, hacer inapropiado al sujeto para el estudio.

E.5 End points

E.5.1

Primary end point(s)

Assess single nucleotide polymorphisms in genes potentially relevant for bosutinib action, metabolism and transport and if there is an association between this and the drug activity and toxicity.

E.5.1.1

Timepoint(s) of evaluation of this end point

End of treatment

Fin de tratamiento

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

End of treatment

Fin de tratamiento

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

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

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

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

Overall survival, progression and other treatments.

Supervivencia global, progresión e inicio de otro tratamiento

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:

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

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

F.4.2.2

In the whole clinical trial

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)

Clinical Practice

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

2015-03-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-28

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials