Clinical Trials Register

Summary
EudraCT Number:	2011-006197-88
Sponsor's Protocol Code Number:	FANCOSTEM-1
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:	2012-01-27
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

2011-006197-88

A.3

Full title of the trial

Clinical Phase II Trial to evaluate efficacy and safety of CD34+ cells mobilization and collection after treatment with plerixafor and filgrastim in patients with Fanconi anemia for subsequent transduction with a lentiviral vector carring FANCA gene and reinfusion in the patient

Ensayo clínico Fase II para evaluar la seguridad y eficacia de la movilización y colecta de células CD34+ tras tratamiento con plerixafor y filgrastim en pacientes con Anemia de Fanconi para su posterior transducción con un vector lentiviral portador del gen FANCA y reinfusión en el paciente

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

FANCOSTEM-1

A.4.1

Sponsor's protocol code number

FANCOSTEM-1

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	Cristina Díaz de Heredia Rubio
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	Cristina Diaz de Heredia Rubio
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	Cristina Díaz de Heredia Rubio
B.5.2	Functional name of contact point	Cristina Díaz de Heredia Rubio
B.5.3	Address:
B.5.3.1	Street Address	Paseo Vall d?Hebron 119-129
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08035
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034934893093
B.5.5	Fax number	0034934893883
B.5.6	E-mail	crdiaz@vhebron.net

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 B.V.
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.3.1	Product name	mozobil
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	110078-46-1
D.3.9.3	Other descriptive name	PLERIXAFOR
D.3.9.4	EV Substance Code	SUB28849
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.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	Neupogen
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
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.3.1	Product name	Neupogen
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	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FILGRASTIM
D.3.9.1	CAS number	121181-53-1
D.3.9.4	EV Substance Code	SUB07627MIG
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	0.6
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

Fanconi anemia

Anemia de Fanconi

E.1.1.1

Medical condition in easily understood language

Fanconi anemia

Anemia de Fanconi

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

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	10055206
E.1.2	Term	Fanconi's anemia
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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 main objective is to assess the safety of cell mobilization after treatment with filgrastim and plerixafor in patients with Fanconi Anemia.

El objetivo principal es determinar la seguridad de la movilización con filgrastim y plerixafor en pacientes diagnosticados de Anemia de Fanconi.

E.2.2

Secondary objectives of the trial

- To assess the efficacy of CD34+ cell mobilization after treatment with filgrastim and plerixafor in patients with Fanconi Anemia.
- To assess the CD34+ collection eficacy after treatment with high doses of filgrastim and plerixafor in patients with Fanconi Anemia.
- To assess the efficacy of the immunomagnetic haematopoietic progenitors selection (CD34+ cells) from the apheresis product

- Determinar la eficacia de movilización de células CD34+ a sangre periférica en pacientes diagnosticados de Anemia de Fanconi tras el tratamiento con filgrastim y plerixafor
- Determinar la eficacia de la colecta de células CD34+ en pacientes diagnosticados de Anemia de Fanconi tras el tratamiento con filgrastim y plerixafor
- Determinar la eficacia de la selección inmunomagnética de progenitores hematopoyéticos (células CD34+) del producto de aféresis

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- male or female > 1 year
- diagnosed of Fanconi's anemia confirmed by instability chromosomal test with diepoxy-butane or mitomycin C
- At least one of the following parameters must be higher than these values: Hemoglobin:8,0 g/dL; neutrophils: 750/mm3; platelets: 30.000/mm3
- Lansky index> 60%.
- Left ventricular ejection fraction >50%.
- To grant informed consent in agreement with current law norms
- Women in childbearing age must obtain a negative result in the pregnancy test in serum or urine in the visit of selection and accept the use of suitable contraceptive methods since at least 14 days prior to the first dose of mobilizing treatment until the 14 days following the last

- Pacientes con diagnóstico de AF confirmado por un test de inestabilidad cromosómica con diepoxibutano o mitomicina C
- Edad> 1 año.
- Al menos uno de los siguientes parámetros debe superar los valores indicados: Hemoglobina:8,0 g/dL; Número de neutrófilos: 750/mm3; Número de plaquetas: 30.000/mm3.
- Índice de Lansky > 60%.
- Fracción de eyección del ventrículo izquierdo >50%.
- Otorgar consentimiento informado de acuerdo con la normativa legal vigente.
- Las mujeres en edad fértil deberán obtener un resultado negativo en la prueba de embarazo en suero o en orina en la visita de selección , y aceptar el empleo de métodos anticonceptivos adecuados al menos desde los 14 días previos a la primera dosis del tratamiento movilizador hasta los 14 días siguientes a la última.

E.4

Principal exclusion criteria

- Evidence of myelodysplastic syndromes or leukemia, or cytogenetic abnormalities predicted of these syndromes in bone marrow aspiration. Cytogenetic analyses performed 2 months before starting study are accepted
- Patients with active infection process or any other underlaying severe medical process
- Severe Functional alteration of organs (hepatic, renal, respiratory)(?3), according to National Cancer Institute (NCI CTCAE v3) criteria
- Haematopoietic transplant
- Any disease or concomitant process that is not compatible with the study as per investigator opinion
- Patients not elegible because of an psico-social evaluation
- Patients that received transfusional support during the last 3 months.
- Pregnant or breastfeeding women

- Evidencias de síndrome mielodisplásico o leucemia, o anomalías citogenéticas predictivas de las mismas en aspirados de médula ósea Estudios citogenéticos realizados con dos meses de antelación se considerarán aceptables.
- Pacientes con proceso infeccioso activo u otro estado médico subyacente grave.
- Alteración funcional de órganos (hepática, renal, respiratorio) grave (?3),según los criterios del National Cancer Institute (NCI CTCAE v3).
- Haber recibido trasplante hematopoyético.
- Toda enfermedad o proceso concomitante que, en opinión del investigador, incapacite al sujeto para su participación en el estudio.
- Pacientes que tras una evaluación psico-social se censuran como no aptos para el procedimiento.
- Haber recibido soporte transfusional en los tres meses previos.
- Mujeres embarazadas o en período de lactancia

E.5 End points

E.5.1

Primary end point(s)

Toxicity of the mobilization procedure according to National Cancer Institute (CTC NCI, versión 3.0)

Toxicidad del protocolo de movilización según los criterios comunes de toxicidad del National Cancer Institute (CTC NCI, versión 3.0)

E.5.1.1

Timepoint(s) of evaluation of this end point

It is anticipated that the patient will receive the medical discharged at the end of the last apheresis. Once the patient is given a medical discharge, hematologic controls are performed at 2 weeks after the last apheresis (in the center where the collection was made), at 2 months, at 6 months and 9 months (in the center of patient referral if your physician is a research trial, or of the collection).

At a year (± 30 days) after the last apheresis, a complete physical examination, blood cell count, basic biochemistry and bone marrow aspirate will be done to the patient in order to control their general health status.

Se prevé que el paciente será dado de alta al finalizar la última aféresis. Una vez dado el paciente de alta médica, se realizarán controles hematológicos a las 2 semanas de la última aféresis (en el centro donde se realizó la colecta), a los 2 meses, a los 6 meses y a los 9 meses (en el centro de referencia del paciente si su médico es investigador del ensayo, o en el de la colecta).

Al año (±30 dias) de realizada la última aféresis, se realizará un examen físico completo, recuento celular sanguíneo, bioquímica básica y un aspirado de la médula ósea del paciente para control.

E.5.2

Secondary end point(s)

- The effectiveness of the mobilization protocol will be determined by the percentage of patients who achieve peripheral blood counts exceeding 5 CD34+ cells /microliter.
- The effectiveness of the CD34+ cell collection protocol will be determined by the percentage of patients who reach at least one million CD34 + cells per kilogram of body weight projected to 5 years after the mobilization process.
- The effectiveness of the of CD34+ cell selection process will be determined by the proportion of immunoselected samples where the recovery of CD34 + cells is at least 50%, and where the final percentage of CD34+ cells is at least 50%.
- The effectiveness of the procedure will be determined by the percentage of patients who reach at least one million CD34 + cells per kilo of weight projected to 5 years after the immunomagnetic selection process of all the collected cells.

- Se determinará la eficacia de la movilización por el porcentaje de pacientes que alcancen en sangre periférica recuentos superiores a 5 células CD34+/microlitro.
- Se determinará la eficacia de la recolección de células CD34+ por el porcentaje de pacientes que alcancen tras las aféresis más de un millón de células CD34+ por kilo de peso proyectado a 5 años tras la movilización.
- Se determinará la eficacia de la selección de células CD34+ del producto obtenido tras aféresis, por el porcentaje de muestras en donde la recuperación de células CD34+ sea superior al 50%, y por el porcentaje final de células CD34+.
-Se determinará la eficacia del procedimiento global por el porcentaje de pacientes que alcancen más de un millón de células CD34+ por kilo de peso proyectado a 5 años, tras la selección inmunomagnética de todas las aféresis realizadas.

E.5.2.1

Timepoint(s) of evaluation of this end point

Última aferesis

Last apheresis

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

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

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

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.8.2.4

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

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

Patients will be excluded or abandon their participation in the study for any of the following reasons:
- Withdrawal of consent by the patient.
- Evidence of disease progression.
- Development of unacceptable toxicity in the investigator's opinion.
- If it is consider relevant to the patient a change in treatment due to loss of clinical benefit, at the discretion of the investigator

Los pacientes serán excluidos ó abandonarán su participación en el estudio por cualquiera de las siguientes razones:
- Retirada del consentimiento por parte del paciente.
- Evidencia de progresión de la enfermedad.
- Desarrollo de toxicidad inaceptable a juicio del investigador.
- Si se considera de interés para el paciente un cambio en el tratamiento por pérdida del beneficio clínico, según el criterio del investigador.

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

Niños

F.3.3.7

Others

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)

Preventional traeatments for Fanconi anemia patients. Probable treatment by gene therapy, genetically correcting their CD34+ cells

Tratamientos preventivos para pacientes con Anemia de Fanconi. Posible tratamiento con terapia génica, corrigiendo genéticamente us células CDE34+

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Red Española de Investigación en Anemia de Fanconi
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Sociedad Española de Hematología y Oncología Pediátrica
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-09

P. End of Trial
P.	End of Trial Status	Completed

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