Clinical Trials Register

Summary
EudraCT Number:	2017-001551-31
Sponsor's Protocol Code Number:	BGB-3111-304
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-12-09
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-001551-31

A.3

Full title of the trial

An International, Phase 3, Open-label, Randomized Study of BGB-3111 Compared with Bendamustine plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Studio internazionale, di fase 3, in aperto, randomizzato di BGB 3111 rispetto a bendamustina più rituximab in pazienti con leucemia linfocitica cronica o piccolo linfoma linfocitico non trattati in precedenza

A.3.1

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

A Phase 3 Study of BGB-3111 Compared with Bendamustine plus Rituximab
in Patients with Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Studio di fase 3 su BGB-3111 rispetto a bendamustina pi¿ rituximab in pazienti con leucemia linfocitica cronica o piccolo linfoma linfocitico non trattati in precedenza

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

BGB-3111-304

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	BEIGENE USA, INC.
B.1.3.4	Country	United States
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	BeiGene, Ltd.
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	BeiGene, Ltd.
B.5.2	Functional name of contact point	US
B.5.3	Address:
B.5.3.1	Street Address	US
B.5.3.2	Town/ city	US
B.5.3.3	Post code	US
B.5.3.4	Country	United States
B.5.4	Telephone number	0
B.5.5	Fax number	0
B.5.6	E-mail	clinicaltrials@beigene.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	BGB-3111
D.3.2	Product code	BGB-3111
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	Zanubrutinib
D.3.9.1	CAS number	1691249-45-2
D.3.9.2	Current sponsor code	BGB-3111
D.3.9.4	EV Substance Code	SUB184615
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	80
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Comparator
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.2.5	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	Bendamustine
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Powder for solution for 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	BENDAMUSTINE HYDROCHLORIDE
D.3.9.1	CAS number	3543-75-7
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB00696MIG
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Comparator
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.2.5	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	Rituximab
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Concentrate for solution for injection
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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB12570MIG
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	10
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Leucemia linfocitica cronica o piccolo linfoma linfocitico non trattati

E.1.1.1

Medical condition in easily understood language

Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Leucemia linfocitica cronica o piccolo linfoma linfocitico

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10041152
E.1.2	Term	Small lymphocytic lymphoma, consistent with CLL (Working Formulation)
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10003946
E.1.2	Term	B-Lymphocytic, CLL (Kiel Classification)
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 compare efficacy between treatment groups in cohort 1, as measured by progression-free survival determined by independent central review

Confrontare l¿efficacia tra i gruppi di trattamento della coorte 1, misurata come sopravvivenza libera da progressione determinata mediante revisione centrale indipendente

E.2.2

Secondary objectives of the trial

To evaluate efficacy in cohort 1, as measured by the following:
o Overall response rate determined by independent central review and
by investigator assessment
o Overall survival
o Duration of response determined by independent central review and by
investigator assessment
o Progression-free survival determined by investigator assessment
o Patient-reported outcomes
¿ To evaluate efficacy in cohort 2 (patients with del17p), as measured
by the following:
o Overall response rate determined by independent central review and investigator
o Overall survival
o Progression-free survival determined by independent central review
o Duration of response determined by independent central review
¿ To compare safety between the treatment groups in cohort 1
¿ To evaluate pharmacokinetics of Zanubrutinib

¿ Valutare l¿efficacia nella coorte 1, misurata in base a quanto segue:
o Tasso di risposta complessiva determinato mediante revisione centrale indipendente e valutazione dello sperimentatore
o Sopravvivenza complessiva
o Durata della risposta determinata mediante revisione centrale indipendente e valutazione dello sperimentatore
o Sopravvivenza libera da progressione determinata mediante valutazione dello sperimentatore
o Esiti riferiti dal paziente
¿ Valutare l¿efficacia nella coorte 2 (pazienti con del17p), misurata in base a quanto segue:
o Tasso di risposta complessiva determinato mediante revisione centrale indipendente e sperimentatore
o Sopravvivenza complessiva
o Sopravvivenza libera da progressione determinata mediante revisione centrale indipendente
o Durata della risposta determinata mediante revisione centrale indipendente
¿ Confrontare la sicurezza tra i gruppi di trattamento della coorte 1
¿ Valutare la farmacocinetica di Zanubrutinib

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients must be unsuitable for treatment with FCR defined as: = 65 years of age at the time of informed consent, OR 18 - 64 years of age and have one or more of the following factors:
a. Cumulative Illness Rating Scale (CIRS) score > 6. A CIRS is not required, it may be used to meet this inclusion requirement.
b. Creatinine clearance < 70 mL/min
c. History of previous serious infection or multiple infections in the past 2 years
2. Confirmed diagnosis of CD20-positive CLL or SLL that meets the CLL criteria (Hallek et al, 2008)
3. Measurable disease by CT/MRI. Measurable disease is defined as = 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular diameters.
4. CLL/SLL requiring treatment
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
6. Life expectancy = 6 months
7. Adequate bone marrow function
8. Patient must have adequate organ function
9. Female patients of childbearing potential must practice highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for = 90 days after the last dose of zanubrutinib, 3 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer.
10. Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for = 90 days after the last dose of
zanubrutinib or 3 months after the last dose of bendamustine whichever is longer.
11. Ability to provide written informed consent and can understand and comply with the requirements of the study

1. I pazienti devono avere = 65 anni di età al momento del consenso informato oppure < 65 anni di età ed essere non idonei alla chemioimmunoterapia con fludarabina, ciclofosfamide e rituximab (FCR) in base a 1 o più dei seguenti fattori: punteggio CIRS > 6], clearance della creatinina < 70 ml/min oppure anamnesi di infezione grave e/o di , infezioni multiple precedenti negli ultimi 2 anni
2. Diagnosi accertata di LLC o SLL positiva per CD-20 che soddisfi i criteri di LLC (Hallek et al., 2008)
3. Malattia misurabile mediante TC / RM. La malattia misurabile è definita come = 1 linfonodo> 1,5 cm nel diametro più lungo e misurabile in 2 diametri perpendicolari.
4. CLL/SLL trattamento richiesto
5. Stato di validità performance del Gruppo cooperativo orientale di oncologia (ECOG) pari a 0, 1 o 2
6. Aspettativa di vita = 6 mesi
6. Funzione del midollo osseo adeguata
7. Il paziente deve avere una funzione organica adeguata
8. Le pazienti in età fertile devono usare metodi anticoncezionali altamente efficaci, da iniziarsi precedentemente alla prima dose del farmaco in studio, per tutta la durata dello studio, e per = 90 giorni dopo l’ultima dose di Zanubrutinib, 3 mesi dopo l’ultima dose di bendamustina o 12 mesi dopo l’ultima dose di rituximab, in base al periodo più lungo.
9. I pazienti sono idonei se sottoposti a vasectomia o se accettano di utilizzare un metodo anticoncezionale di barriera con gli altri metodi descritti sopra durante il periodo del trattamento in studio e per = 90 giorni dopo l’ultima dose di Zanubrutinib o 3 mesi dopo l’ultima dose di bendamustina, in base al periodo più lungo.
10. Capacità di fornire un consenso informato scritto e di comprendere e rispettare i requisiti dello studio.

E.4

Principal exclusion criteria

1. Previous systemic treatment for CLL/SLL
2. Requires ongoing need for corticosteroid treatment. NOTE: Systemic corticosteroids must be fully tapered off/stopped at least 5 days before day of first study drug.
3. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
4. Clinically significant cardiovascular disease
5. Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast, or localized Gleason score 6
prostate cancer.
6. History of severe bleeding disorder
7. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
8. Severe or debilitating pulmonary disease
9. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic
inflammatory bowel disease, or partial or complete bowel obstruction
10. Active fungal, bacterial and/or viral infection requiring systemic therapy
11. Known central nervous system involvement by leukemia or lymphoma
12. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs
13. Known infection with HIV, or serologic status reflecting active hepatitis B or C infection
14. Major surgery within 4 weeks of the first dose of study drug
15. Pregnant or lactating women
16. Vaccination with a live vaccine within 35 days prior to the first dose of study drug
17. Ongoing alcohol or drug addiction
18. Hypersensitivity to zanubrutinib, bendamustine, or rituximab or any of the other ingredients of the study drugs
19. Requires ongoing treatment with a strong CYP3A inhibitor or inducer
19. Concurrent participation in another therapeutic clinical trial.

1. Precedente trattamento sistemico per LLC/SLL
2. Richiede un bisogno continuo di trattamento con corticosteroidi. NOTA: sistemico i corticosteroidi devono essere completamente rastremati / interrotti almeno 5 giorni prima giorno del primo studio farmaco.
3. Leucemia prolinfocitica nota o storia di, o attualmente sospettata,
4. La trasformazione di Richter cardiovascolare clinicamente significativa
5. Diagnosi di tumore maligno negli ultimi 3 anni, ad eccezione del carcinoma cutaneo a cellule basali o squamose trattato in modo curativo, del tumore superficiale della vescica o del carcinoma in situ della cervice uterina o della mammella o punteggio Gleason localizzato 6 cancro alla prostata.
6. Anamnesi di disturbo emorragico grave
6. Anamnesi di ictus o di emorragia intracranica nei 6 mesi precedenti la prima dose del farmaco in studio
7. Malattia polmonare grave o debilitante
8. Incapacità di deglutire le capsule o malattia che colpisce notevolmente la funzione gastrointestinale, come la sindrome da malassorbimento, la resezione dello stomaco o dell’intestino tenue, le procedure di chirurgia bariatrica, la malattia infiammatoria intestinale sintomatica, l’ostruzione intestinale parziale o totale
9. Infezione micotica, batterica e/o virale attiva, che richieda una terapia sistemica
10. Coinvolgimento noto del sistema nervoso centrale da parte della leucemia o del linfoma
11. Condizioni mediche sottostanti che, a giudizio dello sperimentatore, renderebbero pericolosa la somministrazione del farmaco in studio o offuscherebbero l’interpretazione della tossicità o degli eventi avversi
12. Positività per HIV o stato sierologico attestante infezione da epatite B o C attiva
13. Intervento chirurgico di rilievo entro 4 settimane dalla prima dose del farmaco in studio
14. Donne in gravidanza o in allattamento
15. Vaccinazione con un vaccino vivo nei 35 giorni precedenti la prima dose del farmaco in studio
16. Dipendenza in corso da alcol o droghe
17. Ipersensibilità a Zanubrutinib, bendamustina o rituximab o a qualsiasi altro ingrediente dei farmaci in studio
18. Richiede trattamento continuo con un forte inibitore o induttore di CYP3A
19. Partecipazione simultanea a un’altra sperimentazione clinica terapeutica.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is progression-free survival in cohort 1 (patients without del17p) determined by independent central review using the iwCLL guidelines with modification for treatment-related lymphocytosis in patients with CLL and the Revised Criteria for Response for Malignant Lymphoma in patients with SLL, and defined as the time from
randomization to the date of first documentation of disease progression or death, whichever occurs first.

L'endpoint primario è la sopravvivenza libera da progressione nella coorte 1 (pazienti senza del17p) determinato da una revisione centrale indipendente che utilizza il Linee guida iwCLL con modifica per linfocitosi correlata al trattamento in pazienti con CLL e criteri rivisti per risposta per maligna Linfoma in pazienti con SLL e definito come il tempo da randomizzazione alla data della prima documentazione sulla progressione della malattia o morte, a seconda di quale si verifica per primo.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 interim analysis of progression-free survival by independent central review in cohort 1, performed when approximately 79 events (67% of the target number of events at final analysis) from the arms A and B are observed. It is estimated that it will take approximately 25 months to observe 79 events. The final analysis of progression-free survival will
take place after 118 events are observed, which is estimated as approximately 35 months from study start.

Una analisi intermedia della sopravvivenza libera da progressione tramite esame centrale indipendente nella coorte 1, eseguita quando si sono osservati circa 79 eventi (67% dell’obiettivo del numero di eventi all’analisi finale) nei bracci A e B. Si stima che ci vorranno circa 25 mesi per osservare 79 eventi. L’analisi finale della sopravvivenza libera da progressione avverrà dopo l’osservazione di 118 eventi, stimata a circa 35 mesi dall’inizio dello studio.

E.5.2

Secondary end point(s)

- Overall response rate in cohort 1 defined as the proportion of patients
who achieve a complete response, complete response with incomplete
bone marrow recovery, partial response, or partial response with
lymphocytosis, determined by independent central review and by
investigator assessment
- Overall survival in cohort 1 defined as the time from randomization to
the date of death due to any reason
- Duration of response in cohort 1 determined by independent central
review and by investigator assessment using the iwCLL criteria with
modification for treatment-related lymphocytosis, and defined as the
time from the date that response criteria are first met to the date that
disease progression is objectively documented or death, whichever
occurs first
- Progression-free survival in cohort 1 determined by investigator
assessment
- Patient-reported outcomes in cohort 1 measured by the EQ-5D-5L and
EORTC QLQ-C30 questionnaires
- Overall response rate in cohort 2 (patients with del[17p]) determined
by independent central review
- Overall survival in cohort 2
- Progression-free survival in cohort 2 determined by independent
central review
- Duration of response in cohort 2 determined by independent central
review
- Safety parameters, including AEs, SAEs, clinical laboratory tests,
physical exams, and vital signs
- Pharmacokinetic parameters such as apparent clearance of the drug
from plasma (CL/F) and AUC0-12

- Tasso di risposta globale nella coorte 1 definito come la proporzione di pazienti che raggiunge una risposta completa, una risposta completa con recupero incompleto del midollo osseo, una risposta parziale o una risposta parziale con linfocitosi, determinato da un esame centrale indipendente e dalla valutazione dello sperimentatore
- Sopravvivenza globale nella coorte 1 definita come l¿intervallo di tempo tra la randomizzazione e la data del decesso per qualsiasi causa
- Durata della risposta nella coorte 1 determinata da un esame centrale indipendente e dalla valutazione dello sperimentatore, utilizzando i criteri iwCLL con la modifica per la linfocitosi connessa al trattamento, e definita come l¿intervallo di tempo tra la data di soddisfazione iniziale dei criteri di risposta e la data in cui - obiettivamente documentata la progressione della malattia o il decesso, in base all¿evento che si verifica per primo.
- Sopravvivenza libera da progressione nella coorte 1, determinata dalla valutazione dello sperimentatore
- Esiti riferiti dal paziente nella coorte 1, misurati mediante i questionari EQ-5D-5L e EORTC QLQ-C30
- Tasso di risposta globale nella coorte 2 (pazienti con del[17p]), determinato da un esame centrale indipendente
- Sopravvivenza globale nella coorte 2
- Sopravvivenza libera da progressione nella coorte 2, determinata da un esame centrale indipendente
- Durata della risposta nella coorte 2, determinata da un esame centrale indipendente
- Parametri di sicurezza, inclusi eventi avversi, eventi avversi seri, esami clinici di laboratorio, esami obiettivi e segni vitali
- Parametri farmacocinetici, come la clearance apparente del farmaco dal plasma (CL/F) e AUC0-12

E.5.2.1

Timepoint(s) of evaluation of this end point

At time of interim analysis if the PFS comparison between the 2 arms in cohort 1 crosses the stopping boundary. Or at the time of final PFS analysis.

Al momento dell¿analisi intermedia, se il raffronto della PFS tra i 2 bracci nella coorte 1 supera il limite di interruzione. Oppure, al momento dell¿analisi della PFS finale.

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

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)

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

Yes

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

115

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

Information not present in EudraCT

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

Australia

Austria

Belgium

Canada

Czechia

France

Germany

Hungary

Israel

Italy

Korea, Republic of

Netherlands

New Zealand

Poland

Russian Federation

Spain

Sweden

Taiwan

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

LVLS

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:

105

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

445

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

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

294

F.4.2.2

In the whole clinical trial

550

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)

Patients receiving zanubrutinib, who in the opinion of the investigator, continue to benefit from study treatment may continue treatment with zanubrutinib by enrolling on the zanubrutinib Long Term Extension Study.

I pazienti che ricevono zanubrutinib e che, a giudizio dello sperimentatore, continuano a trarre beneficio dal trattamento in studio, possono continuare il trattamento con zanubrutinib arruolandosi nello Studio di estensione a lungo termine su zanubrutinib.

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

2018-02-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-12-14

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

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