Clinical Trials Register

Summary
EudraCT Number:	2016-000297-38
Sponsor's Protocol Code Number:	CL1-68587-003
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:	2018-10-25
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

2016-000297-38

A.3

Full title of the trial

Long-term follow-up study of patients who have previously been exposed to UCART19 (allogeneic engineered T-cells expressing a lentiviral-based anti-CD19 chimeric antigen receptor)

Estudio de seguimiento a largo plazo de pacientes que han sido previamente expuestos a UCART19 (células T alogénicas modificadas que expresan un receptor antigénico quimérico anti-CD19 basado en lentivirus)

A.3.1

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

A study to evaluate the long-term safety of patients with advanced lymphoid malignancies who have been previously administered with UCART19

Estudio para evaluar la seguridad a largo plazo de pacientes con leucemia linfoblástica a los que se les ha administrado UCART19 como terapia previa.

A.4.1

Sponsor's protocol code number

CL1-68587-003

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02735083

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	Institut de Recherches Internationales Servier (I.R.I.S)
B.1.3.4	Country	France
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	ADIR
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institut de Recherches Internationales Servier (I.R.I.S)
B.5.2	Functional name of contact point	Clinical Studies Department
B.5.3	Address:
B.5.3.1	Street Address	50 rue Carnot
B.5.3.2	Town/ city	Suresnes
B.5.3.3	Post code	92284
B.5.3.4	Country	France
B.5.4	Telephone number	+33 155724366
B.5.5	Fax number	+33 155725412
B.5.6	E-mail	clinicaltrials@servier.com
B.Sponsor: 2
B.1.1	Name of Sponsor	Laboratorios Servier S.L.
B.1.3.4	Country	Spain
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	Laboratorios Servier S.L.
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	Laboratorios Servier S. L.
B.5.2	Functional name of contact point	Departamento I+D
B.5.3	Address:
B.5.3.1	Street Address	Avenida de los Madroños 33
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28043
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34917489670
B.5.5	Fax number	+34913003249
B.5.6	E-mail	maria.dequintanabarajas@servier.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	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	UCART19
D.3.2	Product code	S68587
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CD19CAR/RQR8+_TCRαβ-_T-cells
D.3.9.2	Current sponsor code	S68587
D.3.9.3	Other descriptive name	UCART19
D.3.9.4	EV Substance Code	SUB180949
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	600000 to 20000000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
D.3.11.3.5.1	CAT classification and reference number	Gene therapy medicinal product EMA/132648/2014
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	Yes
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

Advanced lymphoid malignancies

Tumores malignos linfoides

E.1.1.1

Medical condition in easily understood language

Advanced lymphoid malignancies

Tumores malignos linfoides

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060390
E.1.2	Term	Leukaemia lymphoblastic acute
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 evaluate the long-term safety of patients with advanced lymphoid malignancies who have been previously administered with UCART19.

Evaluar la seguridad a largo plazo de los pacientes con neoplasias linfoides avanzadas a los que se les ha administrado previamente UCART19.

E.2.2

Secondary objectives of the trial

- To assess the long-term anti leukemic activity (disease outcome, disease-free survival and overall survival),
- To assess the proportion of patients who underwent allogeneic HSCT (Hematopoietic Stem Cell Transplantation),
- To assess the time to transplant,
- To monitor the long-term persistence of UCART19 in blood,
- To monitor the long-term persistence of UCART19 in bone marrow (if a bone marrow aspirate is collected by the centre as part of the routine care of the patient’s disease)

- Evaluar la actividad antileucémica a largo plazo de UCART19 (supervivencia libre de progresión, supervivencia específica de enfermedad),
- Evaluar la proporción de pacientes que son sometidos a un trasplante alogénico de células madre hematopoyéticas (alo-HSCT),
- Evaluar el tiempo hasta el trasplante
- Monitorizar la persistencia a largo plazo de UCART19 en sangre periférica,
- Monitorizar la persistencia a largo plazo de UCART19 en médula ósea (si, como parte del cuidado rutinario del paciente en el centro, se recoge un aspirado de médula ósea

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Written informed consent obtained prior any study-specific procedure (patient or parent(s) or legal representative);
- Patient dosed with UCART19 who completed or discontinued early from a sponsored or from any investigator-initiated study that tested UCART19, or patients who were administered UCART19 under a special access scheme (compassionate use);
- Female patients of childbearing potential and male patients with partners of childbearing potential must continue to use an effective method of birth control as well as their partners.

- Consentimiento informado por escrito obtenido antes de la realización de cualquier procedimiento específico del estudio (paciente, progenitor o representante legal)
- Pacientes que han recibido UCART19 que han completado o abandonado prematuramente un estudio con promotor o cualquier estudio iniciado por un investigador que estudiaba UCART19, o pacientes a quienes se administró UCART19 en el marco de un esquema de acceso especial (uso compasivo)
- En el marco de este estudio, las pacientes femeninas en edad fértil y los pacientes masculinos con parejas en edad fértil deben continuar utilizando un método efectivo de contracepción así como sus parejas,

E.4

Principal exclusion criteria

No exclusion criteria for this study

No hay criterios de exclusión para este estudio

E.5 End points

E.5.1

Primary end point(s)

The safety of UCART19 will be assessed throughout the study by evaluation of the following parameters:
1- Number, duration, outcome of all adverse events (AE)
2- Number, duration, outcome of AE of special interest regardless the relationship with UCART19 and any AE assessed as related to UCART19
3- Number of AEs leading to death
4- For paediatric patients: the potential impact on growth curve and puberty will be assessed by height, weight, Tanner staging and menstrual cycle status
5- If an allo-HSCT is performed, engraftment will be assessed through the reporting of haematological data and chimerism status (if data available from the patient’s medical file)

La seguridad de UCART19 se evaluará a lo largo del estudio, mediante los siguientes parámetros:
1- Número, duración, desenlace de todos los acontecimientos adversos (AEs) ,
2- Número, duración, desenlace de acontecimientos adversos de especial interés al margen de su relación con UCART19 y cualquier AE relacionado con UCART19
3- Número de AEs que conlleven la muerte hasta el final del estudio
4- En pacientes pediátricos se evaluará el potencial impacto sobre la curva de crecimiento y la pubertad mediante la altura, el peso, escala de Tanner y estatus del ciclo menstrual .
5- Si se realiza un trasplante alogénico de células madre hematopoyéticas, se evaluará el éxito del injerto a través de la comunicación de datos hematológicos y del estado de quimerismo (si hay datos disponibles en la historia médica del paciente)
•

E.5.1.1

Timepoint(s) of evaluation of this end point

1- within 12 months post last UCART19 infusion
2- throughout the study
3- up to the end of the study
4- Month 3 post last UCART19 infusion, Month 6 and Month 12, then every 6 months up to Year 3, and yearly until Year 15
5- Up to 3 months post allo-HSCT

1- En los 12 meses que siguen a la última infusión de las UCART19
2- A lo largo de todo el estudio
3- Hasta el final del estudio
4- En el mes 3 , mes 6, mes 12 tras la última infusión de las UCART19, después cada 6 meses hasta el año 3 y una vez al año hasta el año 15
5- Hasta 3 meses post transplante

E.5.2

Secondary end point(s)

- Proportion of patients who relapse or progress among patients who had not relapsed (progression-free survival, disease specific survival)
- Duration of response from the date of first CR or CRi until the date of progression or death due to any cause, whichever occurs first.
- Overall survival (OS)
- Proportion of patients who underwent allogeneic HSCT and time to transplant

- Proporción de pacientes que recaen o progresan versus los pacientes que no progresan (supervivencia libre de progresión, supervivencia específica de la enfermedad),
Duración de la respuesta desde la fecha de CR o CRi hasta la fecha de progresión o muerte debida a cualquier causa, lo que ocurra primero.
-Supervivencia global
- proporción de pacientes que se someten a un trasplante alogénico de células madre hematopoyéticas y tiempo hasta el transplante.

E.5.2.1

Timepoint(s) of evaluation of this end point

M3 post last UCART19 infusion, M6 and M12, then every 6 months up to year 3, and yearly until year 15

M3 tras la última infusión de UCART19, M6, M12 y después cada 6 meses hasta los tres años y una vez al año hasta el año 15

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

Yes

E.7.1.3.1

Other trial type description

Phase I long term follow-up post UCART19 ADMINISTRATION

Estudio de fase I de seguimiento a largo plazo tras administración de UCART19

E.7.2

Therapeutic exploratory (Phase II)

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

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

Belgium

France

United Kingdom

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

LVLS

Ultima visita del último paciente

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

Yes

F.1.1

Number of subjects for this age range:

100

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

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)

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

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

Minor subjects

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

172

F.4.2.2

In the whole clinical trial

200

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)

None

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

2019-01-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-01-18

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

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