Clinical trial NCT06846671: A Study of BGB-16673 Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors
Official title: A Phase 3, Open-Label, Randomized Study of BGB-16673 Compared to Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab or Venetoclax Plus Rituximab Retreatment) in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Both BTK and BCL2 Inhibitors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: CLL
Chronic Lymphocytic Leukemia
Keywords: CLL
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 250
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 purpose of this study is to investigate the efficacy and safety of BGB-16673 compared with investigator's choice (idelalisib plus rituximab \[for CLL only\] or bendamustine plus rituximab or venetoclax plus rituximab retreatment) in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously exposed to both BTK inhibitors (BTKi) and BCL2 inhibitors (BCL2i).

Detailed description: Chronic lymphocytic leukemia is a type of blood cancer that affects people around the world. People with CLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong life and control disease-related symptoms.

In this study, participants with relapsed/refractory (R/R) CLL who were previously exposed to a BTKi and a BCL2i will receive BGB-16673 or the investigator's choice of idelalisib plus rituximab (for CLL only) or bendamustine plus rituximab or venetoclax plus rituximab retreatment. The main purpose of this study is to compare the length of time that participants live without their CLL or SLL worsening between those participants who receive BGB-16673 versus the investigator's choice of treatment (idelalisib plus rituximab or bendamustine plus rituximab, or venetoclax plus rituximab).

Approximately 250 participants will be included in this study around the world. Participants will be randomly allocated to receive either BGB-16673 or the investigator's choice of treatment.

Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of CLL or SLL, requiring treatment, based on 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria.
2. Previously received treatment for CLL/SLL with both a BTKi and a BCL2i.
3. Participants with SLL must have measurable disease by computer tomography (CT)/magnetic resonance imaging (MRI)
4. Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2
5. Adequate liver function
6. Adequate blood clotting function

Exclusion Criteria:

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
2. Prior autologous stem cell transplant or chimeric antigen receptor-T cell therapy in the last 3 months
3. Known central nervous system involvement
4. Prior exposure to any BTK protein degraders
5. Active fungal, bacterial and/or viral infection requiring parenteral systemic therapy
6. Clinically significant cardiovascular disease

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

Primary outcomes:
measure: Progression-Free Survival (PFS) by Independent Review Committee (IRC)
timeFrame: Approximately 36 Months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately 36 Months
measure: Progression-Free Survival (PFS) in Participants with Prior Exposure to Noncovalent Bruton Tyrosine Kinase Inhibitor(s) (ncBTKi) by IRC
timeFrame: Approximately 36 Months
measure: PFS by the Investigator Assessment
timeFrame: Approximately 36 Months
measure: Overall Response Rate (ORR) by IRC and Investigator Assessment
timeFrame: Approximately 36 Months
measure: Rate of Partial Response with Lymphocytosis (PR-L) or Higher Determined by IRC and by Investigator Assessment
timeFrame: Approximately 36 Months
measure: Duration of Response (DOR) by IRC and Investigator Assessment
timeFrame: Approximately 36 Months
measure: Time to Next Anti-CLL/SLL Treatment (TTNT)
timeFrame: Approximately 36 Months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Approximately 36 Months
measure: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire -Core 30 (EORTC QLQ-C30) Global Health Status/QoL (GHS) and Physical Functioning Scales
timeFrame: Approximately 24 Months
measure: Change from baseline in EORTC Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales
timeFrame: Approximately 24 Months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Williams) Usor
state: Colorado
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Hospital
state: Louisiana
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc
state: New York
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: York
country: United States
facility: Cancer Care Associates of York
state: Pennsylvania
city: Tyler
country: United States
facility: Texas Oncology Tyler
state: Texas
city: Caba
country: Argentina
facility: Hospital Aleman
city: Caba
country: Argentina
facility: FUNDALEU
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming (Iaf)
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: West Perth
country: Australia
facility: Perth Blood Institute
state: Western Australia
city: Belo Horizonte
country: Brazil
facility: CETUS
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes Brasilia
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Florianopolis
country: Brazil
facility: Centro de Ensino E Pesquisa Em Oncologia de Santa Catarina (Cepen)
city: Joinville
country: Brazil
facility: Instituto Joinvilense de Hematologia E Oncologia
city: Niteroi
country: Brazil
facility: Complexo Hospitalar de Niteroi
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
city: Rio de Janeiro
country: Brazil
facility: Hospital Sao Lucas Dasa Oncologia
city: Rio de Janeiro
country: Brazil
facility: Oncoclinicas Rio de Janeiro Sa
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: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Vitoria
country: Brazil
facility: Hospital Santa Rita de Cassia Afecc
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Greenfield Park
country: Canada
facility: Centre Integre de Sante Et de Services Sociaux de La Monteregie Centre
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: SaintJerome
country: Canada
facility: Unite de Recherche Clinique Du Cisss Des Laurentides
state: Quebec
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: Augsburg
country: Germany
facility: Klinikum Augsburg, Ii Medizinische Klinik
city: Berlin
country: Germany
facility: Praxis Am Volkspark
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz Ggmbh
city: Frankfurt am Main
country: Germany
facility: Centrum Fur Haematologie Und Onkologie Bethanien
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Homburg
country: Germany
facility: Saarland University Medical Center
city: Koblenz
country: Germany
facility: Invo Institut Fur Versorgungsforschung in Der Onkologie
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig Aor
city: Munster
country: Germany
facility: Universitatsklinikum Munster Medizinische Klinik A
city: Bari
country: Italy
facility: Irccs Istituto Tumori Giovanni Paolo Ii
city: Firenze
country: Italy
facility: Aou Careggi, Servizio Sanitario Toscana
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Novara
country: Italy
facility: Aou Maggiore Della Carita
city: Perugia
country: Italy
facility: Ospedale Santa Maria Della Misericordia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital Clinical Oncology
state: Aichi
city: Chibashi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: MatsuyamaShi
country: Japan
facility: Nho Shikoku Cancer Center
state: Ehime
city: Hiroshimashi
country: Japan
facility: Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital
state: Hiroshima
city: SapporoShi
country: Japan
facility: Aiiku Hospital
state: Hokkaido
city: AmagasakiCity
country: Japan
facility: Hyogo Prefectural Amagasaki General Medical Center
state: Hyogo
city: Kagoshimashi
country: Japan
facility: Kagoshima University Hospital
state: Kagoshima
city: KyotoShi
country: Japan
facility: University Hospital, Kyoto Prefectural Univ of Medicine
state: Kyoto
city: Sendaishi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Niigatashi
country: Japan
facility: Niigata University Medical and Dental Hospital
state: Niigata
city: Kurashikishi
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Kawagoeshi
country: Japan
facility: Saitama Medical Center
state: Saitama
city: Shinagawaku
country: Japan
facility: Ntt Medical Center Tokyo
state: Tokyo
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: SeoGu
country: Korea, Republic of
facility: Dong A University Hospital
state: Busan Gwang'yeogsi
city: JungGu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Daegu Gwang'yeogsi
city: IlsandongGu GoyangSi
country: Korea, Republic of
facility: National Cancer Center (Korea)
state: Gyeonggi-do
city: HwasunGun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-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: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Mexico
country: Mexico
facility: Centro de Investigacion Clinica Gramel
city: Monterrey
country: Mexico
facility: Christus Latam Hub Center of Excellence and Innovation Sc
city: Oaxaca De Juarez
country: Mexico
facility: Centro de Investigacion Clinica de Oaxaca
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Brzozow
country: Poland
facility: Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Krakow
country: Poland
facility: Pratia McM Krakow
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr W Lublinie
city: OD
country: Poland
facility: Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
city: Wrocaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital
city: Ankara
country: Turkey
facility: Gazi University
city: Balcova
country: Turkey
facility: Dokuz Eylul University
city: Dokuma
country: Turkey
facility: Antalya Memorial Hospital
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth and Christchurch Hospitals Nhs Foundation
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals Nhs Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: