Clinical trial NCT06943872: A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL)
Official title: A Phase 3 Randomized, Open-Label, Multicenter Study of Sonrotoclax Plus Anti-CD20 Antibody Therapies Versus Venetoclax Plus Rituximab in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: B-cell lymphoma 2 inhibitor (BCL-2i)
CLL-RR1
German CLL Study Group
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
Collaborators: name: German CLL Study Group
First posted: 2025-04-24
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to compare how well sonrotoclax plus obinutuzumab works versus venetoclax plus rituximab in treating adults with relapsed and/or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study will also compare how well sonrotoclax plus rituximab works versus venetoclax plus rituxumab in treating adults with R/R CLL/SLL. The safety of these treatments will also be assessed.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CLL/SLL that meets the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
* Received one or more prior therapies for CLL/SLL. For each line of therapy, participants must have received at least 2 cycles of the therapy
* Participants with prior BCL2i exposure are eligible if remission duration was ≥3 years with ≥2 years from last BCL2i intake
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
* Adequate organ function

Exclusion Criteria:

* Known active prolymphocytic leukemia or currently suspected Richter's transformation
* Prior autologous stem cell transplantation or chimeric antigen receptor T-cell therapy within 3 months before first dose of study drug
* Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
* Known central nervous system involvement by CLL/SLL
* Severe or debilitating pulmonary disease
* Clinically significant cardiovascular disease

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression-Free Survival (PFS) as assessed by Blinded Independent Review Committee (BIRC) for Arm A versus Arm D
timeFrame: Up to approximately 51 months
Secondary outcomes:
measure: Progression-Free Survival (PFS) as assessed by BIRC for Arm B versus Arm D
timeFrame: Up to approximately 69 months
measure: Rate of uMRD4 for Arm A versus Arm D
timeFrame: Up to approximately 12 months
measure: Complete Response Rate as assessed by BIRC for Arm A versus Arm D
timeFrame: Up to approximately 25 months
measure: Overall Survival for Arm A versus Arm D
timeFrame: Up to approximately 84 months
measure: PFS per Investigator Assessment (INV) for Arm B versus Arm D
timeFrame: Up to approximately 69 months
measure: CRR per BIRC and by INV for Arm B versus Arm D
timeFrame: Up to approximately 25 months
measure: OS for Arm B versus Arm D
timeFrame: Up to approximately 84 months
measure: Rate of uMRD4 for Arm B versus Arm D
timeFrame: Up to approximately 25 months
measure: PFS per BIRC and by INV for Arm A versus Arm B
timeFrame: Up to approximately 69 months
measure: CRR per BIRC and by INV for Arm A versus Arm B
timeFrame: Up to approximately 25 months
measure: OS for Arm A versus Arm B
timeFrame: Up to approximately 84 months
measure: Rate of uMRD4 for Arm A versus Arm B
timeFrame: Up to approximately 25 months
measure: Rate of uMRD4 for Arm A versus Arm D
timeFrame: Up to approximately 25 months
measure: CRR per INV for Arm A versus Arm D
timeFrame: Up to approximately 25 months
measure: PFS per INV for Arm A versus Arm D
timeFrame: Up to approximately 51 months
measure: PFS per INV for Arm C versus Arm D
timeFrame: Up to approximately 69 months
measure: CRR per INV for Arm C versus Arm D
timeFrame: Up to approximately 25 months
measure: OS for Arm C versus Arm D
timeFrame: Up to approximately 84 months
measure: Rate of uMRD4 for Arm C versus Arm D
timeFrame: Up to approximately 25 months
measure: Overall Response Rate (ORR) per BIRC and by INV
timeFrame: Up to approximately 25 months
measure: Duration of Response (DOR) per BIRC and by INV
timeFrame: Up to approximately 69 months
measure: Time to Response (TTR) per BIRC and by INV
timeFrame: Up to approximately 25 months
measure: Time to Next Anti-CLL/SLL Treatment (TTNT)
timeFrame: Up to approximately 84 months
measure: Rate of uMRD4
timeFrame: Up to approximately 25 months
measure: Change from Baseline in the European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Global Health Status/Quality of Life and Physical Functioning Scales
timeFrame: Baseline and up to approximately 69 months
measure: Change from Baseline in EORTC QLQ for Chronic Lymphocytic Leukemia (EORTC QLQ-CLL17) Symptom Burden and Fatigue Scales
timeFrame: Baseline and up to approximately 69 months
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the first dose of study drug(s) to 30 days after the last dose of sonrotoclax or venetoclax, or 90 days after the last dose of obinutuzumab or rituximab; up to approximately 26 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: San Diego
country: United States
facility: Scripps Prebys Cancer Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Williams) Usor
state: Colorado
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists (Niles) Usor
state: Illinois
city: Waukee
country: United States
facility: Mission Cancer and Blood
state: Iowa
city: Louisville
country: United States
facility: University of Louisville, Brown Cancer Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: The Cancer and Hematology Centers
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina At Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials, Llc
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon Willamette Valley Cancer Center
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Upmc Hillman Cancer Center(Univ of Pittsburgh)
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology Baylorcharles A Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Ut Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio Medical Center Usor
state: Texas
city: Tyler
country: United States
facility: Texas Oncology Tyler
state: Texas
city: Vancouver
country: United States
facility: Northwest Cancer Specialist, Pc(Us Oncology Research)
state: Washington
city: Caba
country: Argentina
facility: Hospital Aleman
city: Caba
country: Argentina
facility: FUNDALEU
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming (Iaf)
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Lismore
country: Australia
facility: Northern Nsw Health District
state: New South Wales
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: St Leonards
country: Australia
facility: Genesiscare North Shore
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Private Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast Hospital and Health Service
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Cooloongup
country: Australia
facility: Rockingham Hospital
state: Western Australia
city: West Perth
country: Australia
facility: Perth Blood Institute
state: Western Australia
city: Innsbruck
country: Austria
facility: Landeskrankenhaus Universitaetskliniken Innsbruck
city: Wien
country: Austria
facility: Medical University Vienna Oncology
city: Wien
country: Austria
facility: Hanusch Krankenhaus
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: Uz Antwerpen
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Belo Horizonte
country: Brazil
facility: CETUS
city: Campinas
country: Brazil
facility: Universidade de Campinas Centro de Hematologia E Hemoterapia
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Niteroi
country: Brazil
facility: Complexo Hospitalar de Niteroi
city: Porto Alegre
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia Hospital Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Hospital Sao Lucas
city: Rio de Janeiro
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Rio de Janeiro
city: Salvador
country: Brazil
facility: Hospital Santa Izabel
city: Sao Paulo
country: Brazil
facility: Hospital Samaritano Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Nove de Julho Dasa
city: Sao Paulo
country: Brazil
facility: Instituto Brasileiro de Controle Do Cancer
city: Sao Paulo
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hcfmusp Servico de Hematologia, Hemoterapia E Terapia Celular
city: Vitoria
country: Brazil
facility: Hospital Santa Rita de Cassia Afecc
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency the Vancouver Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancercare Manitoba
state: Manitoba
city: St Johns
country: Canada
facility: Newfoundland and Labrador Health Services
state: Newfoundland and Labrador
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Ciusss Nim Hscm
state: Quebec
city: Calgary
country: Canada
facility: Arthur Je Child Comprehensive Cancer Centre
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Praha
country: Czechia
facility: Ustav Hematologie A Krevni Transfuze (Uhkt)
city: Aalborg
country: Denmark
facility: University Hospital of Aalborg, Denmark
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Roskilde
city: Clermontferrand
country: France
facility: Chu Clermont Ferrand Therapie Cellulaire and Hematolo
city: Nantes
country: France
facility: Centre Hospitalier Universitaire Nantes Hotel Dieu
city: Paris
country: France
facility: Hopital de La Pitie Salpetriere
city: PierreBenite
country: France
facility: Chu Hopital Lyon Sud
city: Reims
country: France
facility: Hopital Robert Debre
city: Rennes Cedes
country: France
facility: Chu Rennes
city: Rouen Cedex
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: Icans Institut de Cancerologie Strasbourg Europe
city: Toulouse
country: France
facility: Iuct Oncopole
city: VandoeuvrelesNancy
country: France
facility: Chu Nancy Hopital Brabois
city: Berlin
country: Germany
facility: Osp Kurfuerstendamm
city: Dresden
country: Germany
facility: Gokos Gmbh
city: Jena
country: Germany
facility: Universitatsklinikum Jena Klinik Fur Innere Medizin Ii
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig Holstein, Campus Kiel
city: Koln
country: Germany
facility: Uniklinik Koeln (Aoer)
city: Munchen
country: Germany
facility: Klinikum Der Universitat Munchen Medizinische Klinik Und Poliklinik Iii
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwabisch Gmund Kliniken Ostalb
city: Neubrandenburg
country: Germany
facility: Dietrich Bonhoeffer Klinikum Neubrandenburg
city: Tubingen
country: Germany
facility: Medizinische Universitaetsklinik
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Wurzburg
country: Germany
facility: Haematologisch Onkologische Schwerpunktpraxis
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: St Jamess Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Di Bari
city: Cagliari
country: Italy
facility: Ao Brotzu Ospedale Oncologico Armando Businco
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
city: Ferrara
country: Italy
facility: Azienda Ospedaliero Universitaria Di Ferrara
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Modena
country: Italy
facility: Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
city: Pagani
country: Italy
facility: Asl Salerno Andrea Tortora
city: SeoGu
country: Korea, Republic of
facility: Pusan National University Hospital
state: Busan Gwang'yeogsi
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: IlsandongGu GoyangSi
country: Korea, Republic of
facility: National Cancer Center (Korea)
state: Gyeonggi-do
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeochoGu
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Hilversum
country: Netherlands
facility: Tergooi Mc
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Gdask
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: OD
country: Poland
facility: Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony Im L Rydygiera W Toruniu
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Uck Wum
city: Wrocaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Hematology
city: Barcelona
country: Spain
facility: Vall D Hebron Institute of Oncology Vhio
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Lhospitalet de Llobregat
country: Spain
facility: Ico Lhospitalet Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Marbella
country: Spain
facility: Costa Del Sol (Marbella, Malaga)
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen de Valme (Sevilla)
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital Hematology
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus I Lund
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Sjukhus
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset Royal Bournemouth Hospital
city: Headington
country: United Kingdom
facility: Churchill Hospital Oxford University Hospital Nhs Trust
city: Leeds
country: United Kingdom
facility: St Jamess University Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: NewCastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: