Clinical Trials Register

Summary
EudraCT Number:	2016-000259-28
Sponsor's Protocol Code Number:	54179060LYM3003
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-04-19
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-000259-28

A.3

Full title of the trial

A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma.

Uno studio randomizzato, in aperto, sulla sicurezza e l'efficacia di ibrutinib in pazienti pediatrici e giovani adulti con linfoma non Hodgkin a cellule B mature recidivante o refrattario.

A.3.1

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

A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma

Uno studio sulla sicurezza e l’efficacia di Ibrutinib in pazienti pediatrici e giovani adulti con linfoma non Hodgkin a cellule B mature recidivante o refrattario

A.4.1

Sponsor's protocol code number

54179060LYM3003

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/252/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
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	Janssen Research & Development, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3171524 21 66
B.5.5	Fax number	+3171524 21 10
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/116/13
D.3 Description of the IMP
D.3.1	Product name	Ibrutinib
D.3.2	Product code	JNJ-54179060
D.3.4	Pharmaceutical form	Capsule, hard
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	Ibrutinib
D.3.9.1	CAS number	936563-96-1
D.3.9.2	Current sponsor code	JNJ-54179060
D.3.9.3	Other descriptive name	IBRUTINIB
D.3.9.4	EV Substance Code	SUB120863
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	140
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	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	Ibrutinib
D.3.2	Product code	JNJ-54179060
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Yes
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	Ibrutinib
D.3.9.1	CAS number	936563-96-1
D.3.9.2	Current sponsor code	JNJ-54179060
D.3.9.3	Other descriptive name	IBRUTINIB
D.3.9.4	EV Substance Code	SUB120863
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	70
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: 3
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	Ibrutinib
D.3.2	Product code	JNJ-54179060
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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	Ibrutinib
D.3.9.1	CAS number	936563-96-1
D.3.9.2	Current sponsor code	JNJ-54179060
D.3.9.3	Other descriptive name	IBRUTINIB
D.3.9.4	EV Substance Code	SUB120863
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	70
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

Mature B-Cell Neoplasm

Neoplasia Cellule B Mature

E.1.1.1

Medical condition in easily understood language

Mature B-Cell Cancer

Tumore Cellule B Mature

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	19.0
E.1.2	Level	HLGT
E.1.2	Classification code	10025320
E.1.2	Term	Lymphomas non-Hodgkin's B-cell
E.1.2	System Organ Class	10005329 - Blood and lymphatic system 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

Part 1:
Confirm that the pharmacokinetics in pediatric subjects is consistent with that in adults

Part 2:
Assess efficacy (EFS) of ibrutinib in combination with RICE or RVICI background therapy compared to RICE or RVICI background therapy alone

PARTE 1:
- Confermare che la farmacocinetica nei soggetti pediatrici è in linea con quella negli adulti
PARTE 2:
- Valutare l'efficacia (sopravvivenza libera da eventi [EFS]) di ibrutinib in combinazione con la terapia di background: RICE o RVICI rispetto alla sola terapia di background: RICE o RVICI

E.2.2

Secondary objectives of the trial

Part 1:
-Evaluate the safety and tolerability of ibrutinib in combination with RICE or RVICI background therapy in pediatric subjects with B-cell malignancies
-Assess anti-tumor activity of ibrutinib as add-on to RICE or RVICI regimens
-Assess disease-specific biomarkers
-Assess the pharmacodynamic response
-Acceptability and palatability assessment of all ibrutinib formulations

Part 2:
-Evaluate the safety and tolerability of ibrutinib in combination with RICE or RVICI background therapy in pediatric subjects and young adults with B-cell malignancies
-Determine the ORR
-Evaluate tumor volume reduction at Day 14
-Determine the number and proportion of subjects who proceed to stem cell transplantation
-Evaluate the time to response
-Measure the duration of response
-Evaluate long-term survival (EFS at 2 and 3 years)
-Evaluate overall survival
-Assess disease-specific biomarkers
For the remaining secondary objectives, please refer to protocol page 28.

Pt 1:Valutare:sicurezza tollerabilità ibrutinib in combinazione con terapia background con RICE o RVICI in soggetti pediatrici con neoplasie maligne a cellule B; attività antitumorale di ibrutinib in aggiunta ai regimi RICE o RVICI;biomarcatori specifici della malattia;risposta farmacodinamica;accettabilità e palatabilità di tutte le formulazioni di ibrutinib.
PT 2: Valutare: sicurezza e tollerabilità di ibrutinib in combinazione con la terapia di background con RICE o RVICI in oggetti pediatrici e giovani adulti con neoplasie maligne a cellule B;riduzione di volume del tumore al Giorno 14;lasso temporale fino alla risposta;sopravvivenza a lungo termine (EFS a 2 e 3 anni);sopravvivenza globale;biomarcatori specifici della malattia;Determinare
tasso di risposta globale (ORR);numero e la proporzione di soggetti che procedono con il trapianto di cellule staminali;Misurare durata della risposta;Per i rimanenti obiettivi secondari si prega di far riferimento alla pagina 28 del protocollo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participants with 1 to less than (<) 18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial diagnosis of mature B-cell non-Hodgkin lymphoma (NHL) occurred at <18 years of age (Part 2 only)
- Participants must be in first or later recurrence or have disease that is primarily refractory to conventional therapy
- Participants must have at least 1 of the following: 1 site of measurable disease greater than (>) 1 centimeter (cm) in the longest diameter by radiological imaging; bone marrow involvement; cerebrospinal fluid with blasts present
- Participants with lansky-Karnofsky score of greater than or equal to (>=) 50
- Adolescent women/young women of childbearing potential must have a negative highly sensitive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening before enrollment/randomization. Adolescent/young women who are pregnant or breastfeeding are ineligible for this study

- Età compresa tra 1 e 18 anni (solo Parte 1) o tra 1 e 30 anni se la diagnosi iniziale di NHL a cellule B mature è avvenuta a un'età <18 anni (solo Parte 2);
- Condizione di prima o successiva ricorrenza o di patologia prevalentemente refrattaria a terapia convenzionale;
- Presenza di almeno uno dei fattori seguenti: sede della malattia misurabile più grande di (>) 1 cm nel diametro più lungo mediante imaging radiologico; coinvolgimento del midollo osseo; liquido cerebrospinale con presenza di blasti;
- Punteggio Lansky-Karnofsky ≥50;
- Le adolescenti/ragazze in età fertile devono presentare un risultato negativo a un test di gravidanza sul siero altamente sensibile o a un test di gravidanza sulle urine (beta-gonadotropina corionica umana, β-hCG) allo screening, prima di arruolamento/randomizzazione. Le adolescenti/ragazze in stato di gravidanza o che allattano al seno non sono idonee allo studio.

E.4

Principal exclusion criteria

- Participants with ongoing anticoagulation treatment with warfarin or
equivalent vitamin K antagonists (example phenprocoumon), or ongoing
treatment with agents known to be strong CYP3A4/5 inhibitors, or has
taken any disallowed therapies as noted in Section 8.2, Prohibited
Medications, before the planned first dose of study drug
- Participants with inherited or acquired bleeding disorders
- Participants with clinically significant arrhythmias, complex congenital
heart disease, or left ventricular ejection fraction (LVEF) <50 percent
(%) or shortening fraction (SF) <=28%
- Participants with known history of human immunodeficiency virus
(HIV) or active Hepatitis B or C virus
- Participants with any condition that could interfere with the absorption
or metabolism of ibrutinib including malabsorption syndrome, disease
significantly affecting gastrointestinal function, or resection of the
stomach or small bowel
- Participants with known allergies, hypersensitivity, or intolerance to
ibrutinib or its excipients (refer to Investigator's Brochure)

- Terapia anticoagulante in corso con warfarin o antagonisti della vitamina K equivalenti (ad es. fenprocumone) oppure terapia in corso con agenti noti per essere forti inibitori del CYP3A4/5 oppure assunzione di terapie non ammesse, come indicato nella sezione 8.2, Farmaci vietati, prima della prima dose prevista del farmaco sperimentale;
- Problemi di sanguinamento ereditari o acquisiti;
- Aritmie clinicamente significative, patologie cardiache congenite complesse oppure frazione di eiezione ventricolare sinistra (LVEF) < 50% o frazione di accorciamento (SF) ≤ 28%;
- Anamnesi nota di virus dell'immunodeficienza umana (HIV) o virus dell'epatite B o C attivo;
- Qualsiasi condizione in grado di interferire con l'assorbimento o il metabolismo di ibrutinib comprese sindrome da malassorbimento, malattia che colpisce significativamente la funzione gastrointestinale o resezione dello stomaco oppure dell'intestino tenue;
- Note allergie, ipersensibilità o intolleranza a ibrutinib o ai suoi eccipienti (fare riferimento all’Investigator’s Brochure).

E.5 End points

E.5.1

Primary end point(s)

1/ Part 1: Area Under The Plasma Concentration-Time Curve (Auc) of Ibrutinib
2/ Part 1: Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib
3/ Part 1: Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib
4/ Part 1: Maximum Observed Plasma Concentration (Cmax)
5/ Part 1: Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size
6/ Part 2: Event-free Survival [EFS]) of Ibrutinib

1/PARTE 1: Esposizione (area sotto la curva concentrazione plasmatica-tempo [AUC]) di Ibrutinib
2/PARTE 1: Clearance plasmatica (CL/F) (orale) apparente di Ibrutinib
3/PARTE 1: volume di distribuzione (Vd/F) (orale) apparente di Ibrutinib
4/PARTE 1: concentrazione plasmatica massima osservata (Cmax)
5/PARTE 1: Relazione fra parametri di farmacocinetica ed età o corporatura
6/PARTE 2: EFS (event free-survival) di Ibrutinib

E.5.1.1

Timepoint(s) of evaluation of this end point

1-4 /Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3.
5/ up to three 28-day cycles
6/ Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (approximately 4.2 years)

End points 1-4 : campioni raccolti prima della dose e 1, 2, 4 e 6 ore dopo la dose nel Giorno 1 e nei Giorni 7 o 8 del ciclo 1; campioni raccolti prima della dose e 1, 2, 4 e 6 ore dopo la dose nel Giorno 1 del ciclo 1 o del ciclo 3
End point 5: fino a 3 cicli di 28 giorni di trattamento
End point 6: dalla randomizzazione alla morte, alla progressione della malattia, o alla mancanza di CR o PR dopo 3 cicli di trattamento (circa 4,2 anni)

E.5.2

Secondary end point(s)

1/ Part 1: Number of Participants with Adverse Events
2/ Part 1: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR)
3/ Part 1: Disease-specific Biomarkers Assessment
4/ Part 1: Bruton’s tyrosine kinase (BTK) Percent Occupancy
5/ Part 1: Visual analog Scale Score for Palatability
6/ Part 2: Number of Participants with Adverse Events
7/ Part 2: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR)
8/ Part 2: Tumor Volume Reduction
9/ Part 2: Percentage of Participants who Proceed to Stem Cell Transplantation
10/ Part 2: Time to Response
11/ Part 2: Duration of Response
12/ Part 2: Percentage of Participants with Long-term Survival
13/ Part 2: Overall Survival
14/ Part 2: Disease-specific Biomarkers Assessment
15/ Part 2: Bruton’s tyrosine kinase (BTK) Percent Occupancy
16/ Part 2: Visual analog Scale Score for Palatability
17/ Part 2: Area under the plasma concentration-time curve (AUC)

1/PARTE 1:numero di soggetti con eventi avversi
2/PARTE 1: Percentuale dei soggetti che ottiene una risposta completa (CR) e una risposta parziale (PR)
3/PARTE 1: Valutazione biomarcatori specifici della malattia
4/PARTE 1: Percentuale di occupazione di bruton tirosin chinasi (BTK)
5/parte 1: Punteggio della scala analogica visiva per palatabilità
6/PARTE 2: numero di partecipanti con eventi avversi
7/PARTE 2: Percentuale dei partecipanti che ottiene una risposta completa (CR) e una risposta parziale (PR)
8/PARTE 2: Riduzione del volume del tumore
9/parte 2: percentuale dei soggetti che procedono con il trapianto di cellule staminali
10/PARTE 2: tempo di risposta
11/PARTE 2: Durata della risposta
12/PARTE 2: percentuale dei soggetti con EFS
13/PARTE 2: sopravvivenza globale
14/PARTE 2: Valutazione biomarcatori specifici della malattia
15/PARTE 2: Percentuale di occupazione di bruton tirosin chinasi (BTK)
16/PARTE 2: Punteggio della scala analogica visiva per palatabilità
17/PARTE 2: Area under the plasma concentration-time curve (AUC)

E.5.2.1

Timepoint(s) of evaluation of this end point

1/ Throughout the study duration (approx up to 4.2yrs)
2/ Treatment Phase:D14 (Cy1),end of Cy2,EOT visit;Post treatment phase:every 12wks for first 12m,every 6m until PD/clinical cutoff for primary endpoint/or upto 2yrs after last subject enrolled,whichever occurs first
3/ Cy1 D1, Cy2 D1, Cy3 D1&EOT visit
4/ 4 hrs postdose on D1 and D7 or 8 of Cy1, predose on Cy2 D1 or Cy3 D1, and the EOT visit
5/ Cy1 D1&y3 D1
6/ Throughout the study duration (approx up to 4.2yrs)
7/ idem timepoint nbr 2
8/ D14
9/ Cy2 (D28)
10-11/ Up to 4.2yrs
12/ 2, 3yrs
13/ Randomization to the date of death (maximum up to 4.2yrs)
14/ Cy1 D1, Cy2 D1, Cy3 D1 and EOT visit
15-16/ Cy1 D1 & Cy3 D1
17/ Predose; 1, 2, and 4 hrs postdose, either on D7 or 8 of Cy1 or on D1 of Cy2 (or Cy3)

1:tutta la durata dello studio;2:fase di trattamento:D14 (Cy1),fine del Cy2, EOT visit; Fase di post trattamento: ogni 12 sett. nei primi 12 mesi, ogni 6 mesi fino a comparsa di PD, cut-off clinico per l'endpoint primario oppure fino a 2 anni dopo l'arruolamento dell'ultimo soggetto, a seconda dell’evento che si verifica per primo;3: C1D1, C2D1, C3D1 e EOT visit;4: 4 h dopo la dose, al D1 e al D7 o 8, prima della dose il C2D1 o C3D1,e alla visita EOT;5:C1D1 e C3D1;6:tutta la durata dello studio (ca 4,2 anni);7:idem timepoint numero 2;8:D14;9: Cy2 (D28);10 e 11:fino a 4,2yrs;12: 2, 3yrs;13:dalla randomizzazione alla data del decesso (massimo fino a 4,2yrs);14: C1D1,C2D1,C3D1 e EOT visit;15 e 16:C1D1 e C3D1;17:prima della dose;1, 2,e 4 h dopo la dose,o il D7 o 8 del C1 o il D1 del C2 o C3.

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

Yes

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

Biomarker analysis

Analisi dei biomarcatori

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Yes

E.8.2.3.1

Comparator description

chemio-immunoterapia di background

Background Chemoimmunotherapy

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

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

Argentina

Belgium

Brazil

Bulgaria

Canada

China

Czech Republic

France

Germany

Hungary

Italy

Japan

Mexico

Netherlands

Poland

Romania

Russian Federation

Spain

Switzerland

Taiwan

Turkey

Ukraine

United Kingdom

United States

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

The end of study is defined as when approximately 60 EFS events have occurred in Part 2 (death, disease progression, or lack of CR or PR after 3 cycles of treatment based on blinded independent event review), or the sponsor terminates the study, whichever comes first.

La fine dello studio viene sancita quando si sono verificati all'incirca 60 eventi EFS nella Parte 2 (decesso, progressione della malattia o mancanza di CR o PR dopo 3 cicli di trattamento sulla base di un'analisi degli eventi indipendente in cieco) oppure lo sponsor termina lo studio, a seconda dell'evento che si verifica per primo.

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