Clinical Trials Register

Summary
EudraCT Number:	2010-019340-40
Sponsor's Protocol Code Number:	MOZ15609
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-10-18
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

Spain - AEMPS

A.2

EudraCT number

2010-019340-40

A.3

Full title of the trial

A Phase 1/2 Combined Dose Ranging and Randomised, Open-label, Comparative Study of the Efficacy and Safety of Plerixafor in Addition to Standard Regimens for Mobilisation of Haematopoietic Stem Cells into Peripheral Blood, and Subsequent Collection by Apheresis, Versus Standard Mobilisation Regimens Alone in Paediatric Patients, Aged 2 to <18 Years, with Solid Tumours Eligible for Autologous Transplants

Estudio combinado de fase 1/2 de búsqueda de dosis y comparativo, abierto, aleatorizado, para evaluar la eficacia y seguridad de plerixafor junto con regímenes estándar para la movilización de células madre hematopoyéticas a sangre periférica, y posterior recolección por aféresis, frente a solo regímenes estándar para la movilización en pacientes pediátricos, de 2 a <18 años, con tumores sólidos que reúnen los requisitos para trasplantes autólogos

A.3.1

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

A Combined Study in Pediatric Cancer Patients for Dose Ranging and Efficacy/Safety of Plerixafor Plus Standard Regimens for Mobilization Versus Standard Regimens Alone

Estudio combinado en pacientes pediátricos con cáncer para evaluar la eficacia y seguridad de plerixafor junto con regímenes estándar para la movilización de células madre frente regímenes estándar solos

A.4.1

Sponsor's protocol code number

MOZ15609

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01288573

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/48/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genzyme Europe B.V.
B.1.3.4	Country	Netherlands
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	Genzyme Europe B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	sanofi-aventis, s.a.
B.5.2	Functional name of contact point	Unidad de Estudios Clínicos
B.5.3	Address:
B.5.3.1	Street Address	c/ Josep Pla nº2
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08019
B.5.3.4	Country	Spain
B.5.4	Telephone number	NA
B.5.5	Fax number	NA
B.5.6	E-mail	ES-unidadestudiosclinicos@sanofi.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	Mozobil
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe BV
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/3/04/227
D.3 Description of the IMP
D.3.1	Product name	Plerixafor
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	plerixafor
D.3.9.1	CAS number	110078-46-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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.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

Paediatric cancer patients (aged 2 to <18 years) with Ewing?s sarcoma/soft tissue sarcoma, neuroblastoma, brain tumours, and all other malignancies (excluding leukaemia) who are planned to undergo high dose chemotherapy followed by autologous haematopoietic stem cell transplantation (HSCT) rescue

Pacientes pediátricos, de 2 a <18 años, con Sarcoma de Ewing/sarcoma de tejidos blandos, neuroblastoma, tumores cerebrales, y todos los otros tumores malignos (con exclusión de la leucemia) que tienen previsto someter a altas dosis de quimioterapia seguido de un transplante autólogo de células madre hematopoyéticas

E.1.1.1

Medical condition in easily understood language

Solid tumours (excluding leukaemia) which will be treated with high dose chemotherapy followed by transplantation of the child's own stem cells.

Tumores sólidos (con exclusión de leucemia) que serán tratados con altas dosis de quimioterapia seguido de un transplante de células madre propias del niño.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to confirm the appropriate dose and efficacy, and to characterise the safety, pharmacokinetics and pharmacodynamics of plerixafor across age and size in paediatric cancer patients when given in addition to standard mobilisation of HSCs into peripheral blood.

El objetivo principal de este estudio es confirmar la dosis adecuada y la eficacia, y caracterizar la seguridad, farmacocinética y farmacodinamia de plerixafor según la edad y el tamaño en pacientes pediátricos con cáncer, cuando se administra junto con el tratamiento habitual para la movilización de células madre hematopoyéticas (haematopoietic stem cells, HSC) a sangre periférica.

E.2.2

Secondary objectives of the trial

The secondary objective of this study is to confirm the efficacy and safety of plerixafor in addition to standard mobilisation of HSCs into peripheral blood, and subsequent collection by apheresis, in paediatric cancer patients.

El objetivo secundario de este estudio es confirmar la eficacia y seguridad de plerixafor añadidoal tratamiento habitual para la movilización de HSC a sangre periférica, y la posterior recolección por aféresis, en pacientes pediátricos con cáncer.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 2 to <18 years
2. Ewing?s sarcoma, soft tissue sarcoma, neuroblastoma, brain tumours or other
malignancy (excluding any form of leukaemia) requiring treatment with high dose
chemotherapy and autologous transplant as rescue therapy
3. Eligible for autologous transplantation
4. Recovered from all acute significant toxic effects of prior chemotherapy
5. Adequate performance status
? for patients ?16 years of age, defined as Karnofsky score >60
? for patients <16 years of age, defined as Lansky score >60
6. Absolute neutrophil count >1.0 × 10P9/L
7. Platelet count >75 × 10P9/L
8. Calculated creatinine clearance (using the Schwartz method):
? during study Stage 1, >80 mL/min/1.73mP2
? during study Stage 2, >60 mL/min/1.73mP2
9. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase
(AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase
(ALT/SGPT) and total bilirubin <3 × upper limit of normal
10. The patient and/or their parent/legal guardian is willing and able to provide signed informed consent

1. Edad de 2 a <18 años
2. Sarcoma de Ewing, sarcoma de tejidos blandos, neuroblastoma, tumores cerebrales u otras neoplasias malignas (excluyendo cualquier forma de leucemia) que requieran tratamiento con quimioterapia a altas dosis y trasplante autólogo como terapia de rescate
3. Apto para trasplante autólogo
4. Recuperado de todos los efectos tóxicos agudos significativos de la quimioterapia previa
5. Estado funcional adecuado
? para pacientes ?16 años, definido como índice de Karnofsky >60
? para pacientes <16 años, definido como índice de Lansky >60
6. Recuento absoluto de neutrófilos >1,0 × 109/l
7. Recuento plaquetario >75 × 109/l
8. Aclaramiento de creatinina calculado (utilizando el método Schwartz):
? durante la Etapa 1 del estudio, >80 ml/min/1,73m2
? durante la Etapa 2 del estudio, >60 ml/min/1,73m2
9. Aspartato aminotransferasa/transaminasa glutámica oxalacética sérica (AST/SGOT), alanina aminotransferasa/transaminasa glutámica pirúvica sérica (ALT/SGPT) y bilirrubina total <3 × límite superior de la normalidad
10. El paciente y/o su padre, madre o tutor legal deberán estar dispuestos y capacitados para proporcionar el consentimiento informado firmado
11. Los pacientes sexualmente activos deben aceptar abstenerse de mantener relaciones sexuales o aceptar utilizar un método anticonceptivo aprobado mientras reciban plerixafor o el tratamiento de movilización estándar y durante al menos 3 meses después de cualquier tratamiento con plerixafor

E.4

Principal exclusion criteria

1. Any form of leukaemia
2. A co-morbid condition which, in the view of the Investigator, renders the patient
at high-risk from treatment complications
3. Previous stem cell transplantation
4. Patients with tumours frequently involving bone marrow (e.g., lymphomas and
neuroblastoma) will be expected to have had evaluation of their marrow as part of
their standard staging evaluations. Persistent high percentage marrow
involvement prior to mobilisation will be prohibited. (Specific guidelines for
different indications are provided in Section 9.2.1 with details of bone marrow
examination requirements at Screening)
5. A residual acute medical condition resulting from prior chemotherapy
6. Acute infection
7. Fever (temperature >38.5°C) - if fever is between 37°C and 38.5°C, infection
must be excluded as a cause
8. Pulse oximetry ?92%
9. Known HIV positive
10. Positive pregnancy test in post pubertal girls
11. History of clinically significant cardiac abnormality or arrhythmia
12. Use of an investigational drug which is not approved in any indication either in
adults or paediatrics within 4 weeks prior to the first dose of G-CSF to be
administered as part of the patient?s planned standard mobilisation regimen,
and/or during the study up until engraftment of the transplant. Drugs approved
for other indications that are being used in a manner considered standard of care
for this transplant procedure are allowed
13. The patient (and/or their parent/legal guardian), in the opinion of the Investigator,
is unable to adhere to the requirements of the study

1. Cualquier forma de leucemia
2. Una enfermedad comórbida que, desde el punto de vista del Investigador, pone al paciente en alto riesgo de sufrir complicaciones derivadas del tratamiento
3. Trasplante de células madre previo
4. Se espera que los pacientes con tumores que suelen afectar a la médula ósea (p. ej., linfomas y neuroblastoma) hayan efectuado una evaluación de la misma como parte de sus evaluaciones de estadificación. La afectación persistente de un alto porcentaje de la médula ósea previo a la movilización estará prohibida.
5. Una afección médica aguda residual como resultado de la quimioterapia previa
6. Infección aguda
7. Fiebre (temperatura >38,5 °C); si la fiebre se sitúa entre 37 °C y 38,5 °C, debe excluirse la infección como causa de la misma
8. Saturación de oxígeno por pulsioximetría ?92 %
9. VIH positivo conocido previamente
10. Prueba de embarazo positiva en niñas postpuberales
11. Antecedentes de arritmia o anomalía cardíaca clínicamente significativas
12. Uso de un fármaco en investigación que no ha sido aprobado para ninguna indicación en adultos o en pacientes pediátricos en las 4 semanas previas a la primera dosis de G-CSF administrada como parte del tratamiento de movilización estándar previsto para el paciente o durante el estudio hasta el injerto del trasplante. Se permite el uso de fármacos aprobados para otras indicaciones que se utilicen de forma estándar para este tipo de trasplante
13. En opinión del Investigador, el paciente (o su padre, madre o tutor legal) no es capaz de cumplir los requisitos del estudio

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint will be the difference between the 2 treatment arms in Stage 2 (comparative part of the study) in the proportion of patients achieving at least a doubling of peripheral blood CD34+ count from the morning of the day preceding the first apheresis day to the morning prior to apheresis.

El criterio de valoración principal de la eficacia será la diferencia entre los 2 brazos de tratamiento en la Etapa 2 (parte comparativa del estudio) en la proporción de pacientes que alcancen por lo menos el doble del recuento de células CD34+ en sangre periférica desde la mañana del día anterior a la primera aféresis hasta la mañana antes de la aféresis.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 5 days

Hasta 5 días

E.5.2

Secondary end point(s)

?Number of days of apheresis required to reach ?2 × 10^6 CD34+ cells/kg [ Time Frame: Up to 5 days ] During Stage 1 and Stage 2
?Yield of CD34+ cells for each apheresis [ Time Frame: Up to 5 days ]
During Stage 1 and Stage 2
?Total CD34+ cell yield [ Time Frame: Up to 5 days ] During Stage 1 and Stage 2
?Percentage of patients proceeding to transplant [ Time Frame: Within 6 months of last apheresis ] During Stage 1 and Stage 2
?Percentage of patients successfully engrafting [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
?Percentage of patients with durable engraftment [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
?Summary of adverse events (AEs) [ Time Frame: Up to 24 months after last transplant or 24 months after last dose (for patients that do not transplant within 6 months of last apheresis) ] During Stage 1 and Stage
2
?Duration of hospitalizations (planned or unplanned) [ Time Frame: Throughout the duration of the study ] During Stage 1 and Stage 2
?Mobilization of tumor cells into peripheral blood [ Time Frame: Up to 5 days ] During Stage 1 and Stage 2
?Relapse rates [ Time Frame: 3, 6, 12 and 24 months post-transplant ]
During Stage 1 and Stage 2
?Occurrence of secondary malignancies [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
?Incidence of primary and secondary graft failure [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
?Time to secondary graft failure [ Time Frame: Up to 24 months posttransplant] During Stage 1 and Stage 2
?Survival rates [ Time Frame: 3, 6, 12 and 24 months post-transplant ]
During Stage 1 and Stage 2

1. Número de días de aféresis necesarios para alcanzar ?2 × 106 células CD34+/kg
2. Producción de células CD34+ por cada aféresis
3. Producción total de células CD34+
4. Porcentaje de pacientes a los que se realiza el trasplante
5. Porcentaje de pacientes con éxito del injerto
6. Porcentaje de pacientes con injerto duradero a los 3, 6, 12 y 24 meses tras el trasplante
7. Incidencia de AA, incluyendo
8. Incidencia de fiebre, neutropenia febril e infecciones
9. Incidencia e intensidad de las reacciones en el sitio de la inyección
10. Duración de las hospitalizaciones (previstas o no) durante el estudio
11. Movilización de las células tumorales a sangre periférica la mañana previa a la aféresis y la mañana de la primera aféresis, y en el producto de la aféresis en la recogida, y justo antes de la infusión (cuando sea posible analizarlo)
12. Tasas de recidivas
13. Frecuencia de neoplasias malignas secundarias
14. Incidencia de fracaso primario y secundario del injerto
15. Tiempo hasta el fracaso secundario del injerto
16. Tasas de supervivencia a los 3, 6, 12 y 24 meses tras el trasplante
17. Recuento de células CD34+ trasplantadas (infundidas)
18. Porcentaje de pacientes con un aumento de 2 veces en el recuento de células CD34+ en sangre periférica Y que alcancen el nivel umbral específico del centro requerido para iniciar la aféresis
19. Aumento en los recuentos de células CD34+ en sangre periférica
20. Volumen de sangre total procesada
21. Tiempo hasta el prendimiento del injerto de neutrófilos (en días)
22. Tiempo hasta el prendimiento del injerto de plaquetas (en días)

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 5 days

Hasta 5 días

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Stage 1 only: dose ranging

Etapa 1 (estudio de escalado de dosis)

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

Stage 1 only: dose ranging

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

Yes

E.8.1.7.1

Other trial design description

Stage 2 only: a comparative randomised study

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

Yes

E.8.2.3.1

Comparator description

Stage 2 only: standard mobilisation treatment

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

Please refer to Protocol

Definida en el Protocolo

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children age 2-18 Parents sign ICF

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)

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

2013-12-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-05-09

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