Clinical trial • Phase III • Oncology

N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3-NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-YL}-7-AZASPIRO[3.5]NONAN-7-YL)-2-[(1H-PYRROLO[2,3-B]PYRIDIN-5-YL)OXY]BENZAMIDE for Previously Untreated Chronic Lymphocytic Leukemia | Chronic lymphocytic leukemia

Phase III trial of N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3-NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-Y…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Previously Untreated Chronic Lymphocytic Leukemia | Chronic lymphocytic leukemia
Trial Stage
Phase III
Drug Modality
Small molecule|Monoclonal antibody

Key dates

Initial CTIS Submission Date
27-10-2023
First CTIS Authorization Date
04-03-2024

Trial design

Randomised, open-label, venetoclax (venclyxto 100 mg film-coated tablets) plus obinutuzumab (gazyvaro 1,000 mg concentrate for solution for infusion). doses/schedules not specified in ctis record.-controlled Phase III trial in Spain, Sweden, Poland and others.

Randomised
Yes
Open Label
Yes
Comparator
Venetoclax (Venclyxto 100 mg film-coated tablets) plus Obinutuzumab (Gazyvaro 1,000 mg concentrate for solution for infusion). Doses/schedules not specified in CTIS record.
Target Sample Size
466

Eligibility

Recruits 466 No vulnerable population selected (isVulnerablePopulationSelected: false). Participants must be aged ≥18 years; informed consent is obtained from participants (adult consent). No assent for minors is applicable because minors are excluded..

Vulnerable Population
No vulnerable population selected (isVulnerablePopulationSelected: false). Participants must be aged ≥18 years; informed consent is obtained from participants (adult consent). No assent for minors is applicable because minors are excluded.

Inclusion criteria

  • {"criterion_text":"- Patients aged ≥ 18 years will have a confirmed diagnosis of CLL, based on Hallek et al 2018, requiring treatment as defined by ≥ 1 of the following: progressive bone marrow failure; massive, progressive, or symptomatic splenomegaly; massive, progressive, or symptomatic lymphadenopathy; progressive lymphocytosis with rapid doubling time; symptomatic or functional extranodal involvement; and/or constitutional symptoms."}

Exclusion criteria

  • {"criterion_text":"- Eligible patients must have ≥ 1 measurable lymph node based on computed tomography/magnetic resonance imaging and no prior systemic treatment for CLL; no history of or known prolymphocytic leukemia or history of, or currently suspected, Richter’s transformation at time of consideration for study; no ongoing clinically significant cardiovascular disease; and no active infection including hepatitis B or C virus or HIV. Patients who require treatment with warfarin or other vitamin K antagonists will be excluded."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Cohort 1: PFS, defined as time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by IRC.","definition_or_measurement_approach":"Time from enrollment to first confirmed disease progression or death; determined by independent review committee (IRC)."}
  • {"endpoint_text":"- Intermediate (Cohort 1): Undetectable minimal residual disease at < 10^-4 sensitivity (uMRD4) rate at the first Post-treatment Follow-up (PTFU1) Visit based on next-generation sequencing (NGS [clonoSEQ]).","definition_or_measurement_approach":"uMRD4 measured at first post-treatment follow-up (PTFU1) using next-generation sequencing (NGS, clonoSEQ) with sensitivity <10^-4."}

Secondary endpoints

  • {"endpoint_text":"- Cohort 1: Overall complete response rate (CRR) defined as the proportion of patients that achieved best response of CR/CRi, determined by IRC.","definition_or_measurement_approach":"Proportion of patients achieving best response of CR or CRi as determined by independent review committee (IRC)."}
  • {"endpoint_text":"- Cohort 1: OS, defined as time from the date of enrollment to the date of death because of any cause","definition_or_measurement_approach":"Time from enrollment to death from any cause (overall survival, OS)."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
466
Recruitment Window Months
99
Consent Approach
Informed consent obtained from participants (adults ≥18). Subject information and ICF documents provided; ICF materials available in multiple languages (documents list includes EN, DE, FR, IT, NL, PL, CZ, ES, SE). Consent is provided by the participant; no assent for minors because study excludes participants <18.

Geography

Total Number Of Sites
55
Total Number Of Participants
206

Spain

Earliest CTIS Part Ii Submission Date
23-02-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
781
Number Of Sites
8
Number Of Participants
22

Sites

Site Name
Institut Catala D'oncologia
Department Name
Hematology
Contact Person Name
Eva González Barca
Contact Person Email
e.gonzalez@iconcologia.net
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Hematology
Contact Person Name
Javier López Jiménez
Contact Person Email
jljimenez@salud.madrid.org
Site Name
Hospital Universitario La Paz
Department Name
Hematology
Contact Person Name
Patricia Baltasar Tello
Contact Person Email
XXXXX@XXXX.XX
Site Name
Hospital Universitario 12 De Octubre
Department Name
Hematology
Contact Person Name
Javier de La Serna
Contact Person Email
javier.serna@salud.madrid.org
Site Name
Hospital Universitario Nuestra Senora De Candelaria
Department Name
Hematology and Hemotherapy
Contact Person Name
Carmen Marrero Santos
Contact Person Email
XXXXX@XXXX.XX
Site Name
El Hospital Universitario De Gran Canaria Dr. Negrin
Department Name
Hematology
Contact Person Name
Alexia Suárez Cabrera
Contact Person Email
asuacab@gobiernodecanarias.org
Site Name
MD Anderson Cancer Center
Department Name
Hematology
Contact Person Name
Adolfo de la Fuente
Contact Person Email
afuente@mdanderson.es
Site Name
Hospital Universitario De Burgos
Department Name
Hematology and Hemotherapy
Contact Person Name
Francisco Javier Díaz Gálvez
Contact Person Email
fcdiaz@saludcastillayleon.es

Sweden

Earliest CTIS Part Ii Submission Date
08-05-2024
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
701
Number Of Sites
1
Number Of Participants
12

Sites

Site Name
Karolinska University Hospital
Department Name
Cancerstudieenheten
Contact Person Name
Anders Österborg
Contact Person Email
xxxx.xxx@regionstockholm.se

Poland

Earliest CTIS Part Ii Submission Date
14-02-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
789
Number Of Sites
6
Number Of Participants
30

Sites

Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
Contact Person Name
Tomasz Wrobel
Contact Person Email
XX@XX
Site Name
Instytut Hematologii I Transfuzjologii
Department Name
Klinika Hematologii, Poradnia Hematologiczna
Contact Person Name
Ewa Lech-Maranda
Contact Person Email
emaranda@ihit.waw.pl
Site Name
Uniwersytecki Szpital Kliniczny Nr 4 W Lublinie
Contact Person Name
Krzysztof Giannopoulos
Contact Person Email
XX@XX
Site Name
Uniwersytecki Szpital Kliniczny W Poznaniu
Department Name
Oddzial Hematologii i Transplantacji Szpiku, Poradnia Hematologiczna
Contact Person Name
Lidia Gil
Contact Person Email
lidia.gil@skpp.edu.pl
Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Oddział Hematologii Ogolnej i Chorob Wewnetrznych
Contact Person Name
Tadeusz Robak
Contact Person Email
robaktad@csk.umed.lodz.pl
Site Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Department Name
CSK Klinika Hematologii, Transplantologii i Chorob Wewnetrznych, Poradnia Hematologiczna
Contact Person Name
Krzysztof Jamroziak
Contact Person Email
k.jamroziak@wum.edu.pl

Czechia

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
790
Number Of Sites
6
Number Of Participants
30

Sites

Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
I. interní klinika - klinika hematologie 1.LF a VFN
Contact Person Name
Martin Spacek
Contact Person Email
xxxx@vfn.cz
Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
4.interní hematologická klinika
Contact Person Name
Martin Simkovic
Contact Person Email
xxx@fnhk.cz
Site Name
Fakultni Nemocnice Brno
Department Name
Interní hematologická a onkologická klinika
Contact Person Name
Michael Doubek
Contact Person Email
xxxxx@fnbrno.cz
Site Name
Fakultni Nemocnice Ostrava
Department Name
Klinika hematoonkologie
Contact Person Name
Jana Mihalyova
Contact Person Email
xxx@fno.cz
Site Name
University Hospital Olomouc
Department Name
Hemato-onkologická klinika
Contact Person Name
Zuzana Kubova
Contact Person Email
xxxx@fnol.cz
Site Name
Fakultni Nemocnice Plzen
Department Name
Hematologicko-onkologické oddělení FN Plzeň
Contact Person Name
Daniel Lysak
Contact Person Email
xxxx@fnplzen.cz

Netherlands

Earliest CTIS Part Ii Submission Date
14-02-2024
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
786
Number Of Sites
8
Number Of Participants
26

Sites

Site Name
Amsterdam UMC
Department Name
Hematology
Contact Person Name
Arnon Kater
Contact Person Email
ctis@amsterdamumc.nl
Site Name
Stichting Martini Ziekenhuis
Department Name
Wetenschappelijk instituut
Contact Person Name
John Schreurs
Contact Person Email
j.schreurs@mzh.nl
Site Name
Haga Hospital
Department Name
Hematology
Contact Person Name
Sabina Kersting
Contact Person Email
s.kersting@hagaziekenhuis.nl
Site Name
Noordwest Ziekenhuisgroep Stichting
Department Name
Hematology
Contact Person Name
Hein Visser
Contact Person Email
h.visser@nwz.nl
Site Name
Albert Schweitzer Ziekenhuis
Department Name
Hematology
Contact Person Name
Mark-David Levin
Contact Person Email
m-d.levin@asz.nl
Site Name
Sint Franciscus Vlietland Groep Stichting
Department Name
Hematology
Contact Person Name
Henk-Jan Boiten
Contact Person Email
h.boiten@franciscus.nl
Site Name
Ikazia Ziekenhuis
Department Name
Hematology
Contact Person Name
Fransien De Boer
Contact Person Email
fr.de.boer@ikazia.nl
Site Name
Meander Medisch Centrum
Department Name
Hematology
Contact Person Name
Josien Regelink
Contact Person Email
JC.regelink@meandermc.nl

Italy

Earliest CTIS Part Ii Submission Date
16-02-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
787
Number Of Sites
7
Number Of Participants
22

Sites

Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Hematology
Contact Person Name
Annamaria Frustaci
Site Name
Hospital Santa Maria Della Misericordia
Department Name
Medicine and Surgery
Contact Person Name
Paolo Sportoletti
Contact Person Email
paolo.sportoletti@unipg.it
Site Name
Azienda Unita Sanitaria Locale Di Bologna
Department Name
oncological and hematological diseases
Contact Person Name
Pier Luigi Zinzani
Contact Person Email
pierluigi.zinzani@unibo.it
Site Name
Azienda Ospedale-Universita Padova
Department Name
Hematology
Contact Person Name
Andrea Visentin
Contact Person Email
andrea.visentin@aopd.veneto.it
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
Division of Hematology
Contact Person Name
Gianluca Gaidano
Contact Person Email
gianluca.gaidano@med.uniupo.it
Site Name
University Hospital Of Ferrara
Department Name
Hematology Oncology
Contact Person Name
Antonio Cuneo
Contact Person Email
cut@unife.it
Site Name
European Institute Of Oncology S.r.l.
Department Name
Oncohematology Deparment
Contact Person Name
Enrico Derenzini
Contact Person Email
enrico.derenzini@ieo.it

Germany

Earliest CTIS Part Ii Submission Date
07-05-2024
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
703
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Centrum für Hämatologie und Onkologie Bethanien
Contact Person Name
Christian Johannes Schmitt
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Hämatologie und Onkologie
Contact Person Name
Niklas Gebauer
Contact Person Email
xxx@uksh.de
Site Name
IQVIA
Contact Person Name
Jan-Piet Habbel

France

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
798
Number Of Sites
13
Number Of Participants
39

Sites

Site Name
University Hospital Of Clermont-Ferrand
Department Name
Thérapie Cellulaire et Hématologie
Contact Person Name
Romain GUIEZE
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Hématologie et Thérapie Cellulaire
Contact Person Name
Caroline DARTIGEAS
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
L'Hopital Prive Du Confluent
Department Name
Hématologie
Contact Person Name
Katell LE DU
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Hématologie Clinique
Contact Person Name
Anne LOK
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Hématologie Clinique
Contact Person Name
Damien ROOS-WEIL
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
CHRU De Nancy
Department Name
Hématologie Médecine Interne
Contact Person Name
Pierre FEUGIER
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Hématologie
Contact Person Name
Caroline DARTIGEAS
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Leon Berard
Department Name
Oncologie Médicale
Contact Person Name
Anne-Sophie MICHALLET
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Hospitalier Le Mans
Department Name
Hématologie
Contact Person Name
Kamel LARIBI
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Institut Bergonie
Department Name
Hématologie
Contact Person Name
Fontanet BIJOU
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Maladies du Sang
Contact Person Name
Doriane CAVALIERI
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Centre Henri Becquerel
Department Name
Hématologie
Contact Person Name
Stephane LEPRETRE
Contact Person Email
xxxxxx@xxxxxxx.fr
Site Name
Clinique Louis Pasteur
Department Name
Oncologie
Contact Person Name
Serge BOLOGNA
Contact Person Email
xxxxxx@xxxxxxx.fr

Austria

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
794
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
SCRI CCCIT Ges.m.b.H.
Department Name
University Clinic for Internal Medicine III
Contact Person Name
Alexander Egle
Contact Person Email
a.egle@salk.at
Site Name
Medizinische Universitaet Innsbruck
Department Name
Internal Medicine V, Hematology and Oncology
Contact Person Name
Jan-Paul Bohn
Contact Person Email
jan-paul.bohn@i-med.ac.at
Site Name
Hanusch Krankenhaus Der Wiener Gebietskrankenkasse
Department Name
3rd Medical Department for Hematology and Oncology
Contact Person Name
Thomas Nösslinger
Contact Person Email
thomas.noesslinger@oegk.at

Sponsor

Primary sponsor

Full Name
BeOne Medicines AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Medidata Solutions International Limited
Responsibilities
E-data capture
Name
PPD (UK) Limited
Responsibilities
Safety reporting
Name
Iqvia Biotech LLC
Responsibilities
Administrative
Name
Bioclinica Shanghai Co. Ltd.
Responsibilities
Medical Image Analysis/Review
Name
Scout Clinical
Responsibilities
Patient travel reimbursement

Third parties

  • {"country":"United States","full_name":"Laboratory Corporation Of America Holdings","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Clinical Supply Vendor","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"E-data capture","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Quipment","duties_or_roles":"code 14","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Predicine Inc.","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient travel reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"China","full_name":"Wuxi Apptec Co. Ltd.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ledger Run Inc.","duties_or_roles":"Administrative","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"Administrative","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Bioclinica Shanghai Co. Ltd.","duties_or_roles":"Medical Image Analysis/Review","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"PPD (UK) Limited","duties_or_roles":"Safety reporting","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"MLL Dx GmbH","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Almac","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"Clinical Supply Vendor","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Labcorp Pharmaceutical Research And Development (Shanghai) Co. Ltd.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Singapore","full_name":"Zuellig Pharma Specialty Solutions Group Pte. Ltd.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"LabPMM, GmbH","duties_or_roles":"code 4","organisation_type":"Industry"}
  • {"country":"Ireland","full_name":"Thermo Fisher Scientific Cork Limited","duties_or_roles":"Prophylaxis Product Supply","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Burning Rock Dx LLC","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH (alternate entry)","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"NGS MRD; code 4","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BGB-11417
Active Substance
N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3-NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-YL}-7-AZASPIRO[3.5]NONAN-7-YL)-2-[(1H-PYRROLO[2,3-B]PYRIDIN-5-YL)OXY]BENZAMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Investigational (not authorised)
Maximum Dose
320 mg
Investigational Product Name
Zanubrutinib (BGB-3111)
Active Substance
ZANUBRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Investigational (not authorised)
Maximum Dose
320 mg
Investigational Product Name
Venclyxto (Venetoclax) 100 mg film-coated tablets
Active Substance
VENETOCLAX
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketing authorisation)
Maximum Dose
400 mg
Investigational Product Name
Gazyvaro (Obinutuzumab) 1,000 mg concentrate for solution for infusion
Active Substance
OBINUTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
CONCENTRATE FOR SOLUTION FOR INFUSION
Route
INFUSION
Authorisation Status
Authorised (marketing authorisation)
Maximum Dose
1000 mg
Combination Treatment
Yes

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