A Study of Zanubrutinib Plus Anti-CD20 Versus Lenalidomide Plus Rituximab in Participants With Relapsed/Refractory Follicular or Marginal Zone Lymphoma

Marginal Zone Lymphoma Clinical Trial

— MAHOGANY  

Official title:

A Phase 3 Randomized, Open-Label Multicenter Study of Zanubrutinib (BGB-3111) Plus Anti-CD20 Antibodies Versus Lenalidomide Plus Rituximab in Patients With Relapsed/Refractory Follicular or Marginal Zone Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05100862
• Other study ID #: BGB-3111-308
• Secondary ID: CTR202325452022-
• Status: Recruiting
• Phase: Phase 3
• Start date: March 10, 2022
• Est. completion date: June 2030

Study information

• Verified date: June 2024
• Source: BeiGene
• Contact: Study Director BeiGene
• Phone: 1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare the efficacy of zanubrutinib plus obinutuzumab versus lenalidomide plus rituximab (R^2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL), as measured by progression-free survival as determined by an independent review committee in accordance with the 2014 modification of the International Working Group on non-Hodgkin lymphoma (NHL) Criteria based on n positron emission tomography and computed tomography (PET/CT), and to compare the efficacy of zanubrutinib plus rituximab versus R^2 in participants with R/R marginal zone lymphoma (MZL), as measured by progression free survival (PFS) assessed by IRC in accordance with CT-based Lugano 2014 Criteria.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: June 2030
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically confirmed grade 1-3a FL or MZL
• Previously treated with = 1 line of systemic therapy including anti-CD20 agent. Must have a documented failure to achieve at least partial response during the most recent systemic therapy or documented progressive disease after the most recent systemic therapy
• Need for systemic therapy for FL or MZL
• Measurable disease by computed tomography or magnetic resonance imaging
• Adequate bone marrow, liver and renal function

Key Exclusion Criteria:

• Transformation to aggressive lymphoma
• Requiring ongoing need for corticosteroid treatment
• Clinically significant cardiovascular disease
• Prior malignancy within the past 2 years
• Active fungal, bacterial, and/or viral infection that requires systemic therapy Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Marginal Zone Lymphoma
• Relapsed/Refractory Follicular Lymphoma

Intervention

Drug:
• Zanubrutinib
Zanubrutinib will be administered orally as two 80-milligram (mg) capsules twice a day (160 mg twice a day) or four 80-mg capsules once a day (320 mg once a day) continuously in repeated 28-day cycles.
• Rituximab
Rituximab will be administered intravenously at a dose of 375 mg/meter squared on Days 1, 8, 15, and 22 of Cycle 1 and on Day 1 of Cycles 2 to 5. Each cycle is 28 days in length.
• Lenalidomide
Lenalidomide will be administered orally as 20-mg capsules (10 mg if creatinine clearance = 30 mL/min but < 60 mL/min) once a day on Days 1 to 21 of each 28-day cycle for a total of 12 cycles.
• Obinutuzumab
Obinutuzumab will be administered at a dose of 1000 mg on Cycle 1 Days 1, 8, 15 and then on Cycles 2 to 6 Day 1.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Aleman	Caba
Australia	Sunshine Coast Hospital and Health Service	Birtinya	Queensland
Australia	Monash Health	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Townsville University Hospital	Douglas	Queensland
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	Cabrini Hospital Malvern	Malvern	Victoria
Australia	Epworth Freemasons	Melbourne	Victoria
Australia	La Trobe Regional Hospital	Melbourne
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Orange Health Hospital	Orange	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	Perth Blood Institute	West Perth	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Uk St Poelten	St Poelten
Austria	Medical Univeristy Vienna	Wien
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Az Sint Jan Brugge	Brugge
Belgium	Universitair Ziekenhuis Gent	Gent
Brazil	Hospital de Amor Barretos	Barretos
Brazil	Clinica de Oncologia Reichow	Blumenau
Brazil	Unesp Faculdade de Medicina Da Universidade Estadual Paulista Campus Botucatu	Botucatu
Brazil	Instituto Dor de Pesquisa E Ensino Distrito Federal	Brasilia
Brazil	Universidade de Campinas Centro de Hematologia E Hemoterapia	Campinas
Brazil	Fundacao Universidade de Caxias Do Sul	Caxias do Sul
Brazil	Centro Integrado de Oncologia de Curitiba Ss Cionc	Curitiba
Brazil	Hospital Erasto Gaertner	Curitiba
Brazil	Centro de Ensino E Pesquisa Em Oncologia de Santa Catarina (Cepen)	Florianopolis
Brazil	Centro Gaucho Integrado de Oncologia Hospital Mae de Deus	Porto Alegre
Brazil	Hospital Ernesto Dornelles	Porto Alegre
Brazil	Hospital de Amor Amazonia	Porto Velho
Brazil	Instituto Dor de Pesquisa E Ensino	Recife
Brazil	Instituto Dor de Pesquisa E Ensino Pernambuco	Recife
Brazil	Hospital Das Clinicas Da Faculdade de Medicina de Ribeirao Preto Usp	Ribeirao Preto
Brazil	Complexo Hospitalar de Niteroi	Rio de Janeiro
Brazil	Instituto Americas Ensino, Pesquisa E Inovacao	Rio de Janeiro
Brazil	Oncoclinicas Rio de Janeiro Sa	Rio de Janeiro
Brazil	Ensino E Terapia de Inovacao Clinica Amo Etica	Salvador
Brazil	Hospital Sao Rafaelinstituto Dor de Pesquisa E Ensino	Salvador
Brazil	Hcfmusp Servico de Hematologia, Hemoterapia E Terapia Celular	Sao Paulo
Brazil	Hospital Nove de Julho Dasa	Sao Paulo
Brazil	Instituto Dor de Pesquisa E Ensino Sao Paulo	Sao Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	Sao Paulo
Brazil	Hospital Santa Rita de Cassia Afecc	Vitoria
China	Anyang Cancer Hospital	Anyang	Henan
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University(Tongzhou)	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	The First Peoples Hospital of Changde City	Changde	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Dongyang Peoples Hospital	Dongyang	Zhejiang
China	Foshan First Peoples Hospital	Foshan	Guangdong
China	Sun Yat Sen University Cancer Center	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Huizhou Central Peoples Hospital	Huizhou	Guangdong
China	The First Hospital of Jiaxing	Jiaxing	Zhejiang
China	Jinhua Municipal Central Hospital	Jinhua	Zhejiang
China	Meizhou People Hospital	Meizhou	Guangdong
China	Jiangxi Province Cancer Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Peoples Hospital of Rizhao	Rizhao	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The Second Affiliated Hospital of Shandong First Medical University	Taian	Shandong
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Wannan Medical College	Wuhu	Anhui
China	Wuxi Peoples Hospital	Wuxi	Jiangsu
China	Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong
China	Henan Cancer Hospital	Zhengzhou	Henan
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni Nemocnice Olomouc	Olomouc
France	Hopital Prive Dantony, Departement Dhemathologie	Antony
France	Centre Hospitalier Le Mans	Le Mans
France	Chu Montpellier Hopital Saint Eloi	Montpellier Cedex
France	Hopital Larchet Chu Nice	Nice
France	Institut Curie	Paris
France	Necker University Hospital	Paris
France	Icans Institut de Cancerologie Strasbourg Europe	Strasbourg
France	Chu Nancy Hopital Brabois	VandoeuvrelesNancy
Georgia	High Technology Hospital Medcenter Ltd	Batumi
Georgia	JSC VIAN	Kutaisi
Georgia	Oncology Research Center Ltd	Tbilisi
Ireland	St Jamess Hospital	Dublin
Ireland	University Hospital Waterford	Waterford
Israel	Haemek Medical Center	Afula
Israel	Assuta Ashdod Medical Center	Ashdod
Israel	Hadassah En Karem Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat gan
Israel	Assuta Medical Center	Tel Aviv
Italy	Cro Irccs Aviano	Aviano
Italy	Irccs Azienda Ospedaliero Universitaria Bologna	Bologna
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Istituto Europeo Di Oncologia	Milano
Italy	Aou Maggiore Della Carita	Novara
Italy	Azienda Ospedaliera Di Padova	Padova
Italy	Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi	Pavia
Italy	Arcispedale S Maria Nuova Ausl Reggio Emilia Hematology Unit	Reggio Emilia
Italy	Aou Santa Maria Della Misericordia Di Udine	Udine
Italy	Ospedale Di Circolo E Fondazione Macchi	Varese
Korea, Republic of	Dong A University Hospital	Busan	Busan Gwang'yeogsi
Korea, Republic of	Inje University Busan Paik Hospital	Busan	Busan Gwang'yeogsi
Korea, Republic of	Pusan National University Hospital	Busan	Busan Gwang'yeogsi
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu	Gyeongsangbukdo
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasungun	Jeonranamdo
Korea, Republic of	Gyeongsang National University Hospital	Jinjusi	Gyeongsangnamdo
Korea, Republic of	Seoul National University Bundang Hospital	Seongnamsi	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Korea University Anam Hospital	Seoul	Gyeonggido
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Soon Chun Hyang University Hospital Seoul	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea, Seoul St Marys Hospital	Seoul	Seoul Teugbyeolsi
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia McM Krakow	Krakow
Portugal	Unidade Local de Saude Almada Seixal	Almada
Portugal	Instituto Portugues de Oncologia Do Porto Francisco Gentil, Epe	Porto
Portugal	Unidade Local de Saude Gaia E Espinho	VILA NOVA DE GAIA Porto
Puerto Rico	Pan American Oncology Trials, Llc	Rio Piedras
Puerto Rico	Auxilio Mutuo Cancer Center	San Juan
Romania	Coltea Clinical Hospital	Bucharest
Romania	Institutul Oncologic Prof Dr Ion Chiricuta Cluj Napoca	ClujNapoca
Romania	Institutul Regional de Oncologie Iasi	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Bihor	Oradea
Spain	Ico Badalona	Badalona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital Universitario Puerta Del Mar	Cadiz
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Institut Catala Doncologia Hospital Duran I Reynals	Hospitalet de LLobregat
Spain	Complejo Asistencial Universitario de Leon	Leon
Spain	Clinica Universidad de Navarra	Madrid
Spain	H Puerta de Hierro Majadahonda	Madrid
Spain	Hospital de La Princesa	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Hospital Clinico Universitario Virgen de La Arrixaca	Murcia
Spain	Clinica Universidad de Navarra Pamplona	Pamplona
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitari Mutua Terrassa	Terassa
Switzerland	Hfr Fribourg	Fribourg
Switzerland	Reseau Hospitalier Neuchatelois	La ChauxdeFonds
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	The Christie Hospital	Greater Manchester
United Kingdom	Huddersfield Royal Infirmary	Huddersfield
United Kingdom	Nhs Highland	Inverness
United Kingdom	The Leeds Teaching Hospitals Nhs Trust	Leeds
United Kingdom	University College Hospital	London
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Southampton General Hospital	Southampton
United States	Luminis Health Anne Arundel Medical Center	Annapolis	Maryland
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	American Oncology Partners of Maryland Pa	Bethesda	Maryland
United States	St Vincent Frontier Cancer Center	Billings	Montana
United States	Va Northeast Ohio Healthcare System	Cleveland	Ohio
United States	University of Missouri Hospital, Ellis Fischel Cancer Center	Columbia	Missouri
United States	Texas Oncology Baylorcharles A Sammons Cancer Center	Dallas	Texas
United States	Mission Cancer and Blood	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Summit Medical Group	Florham Park	New Jersey
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Nebraska Cancer Specialists	Grand Island	Nebraska
United States	Nebraska Cancer Specialists (Satellite Site)	Grand Island	Nebraska
United States	Corewell Health the Michigan Cancer Consortium	Grand Rapids	Michigan
United States	Hattiesburg Hematology and Oncology Clinic	Hattiesburg	Mississippi
United States	Md Anderson Cancer Center	Houston	Texas
United States	Kaiser Permanente Southern California	Irvine	California
United States	Baptist Md Anderson Cancer Center	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Los Angeles Cancer Network	Los Angeles	California
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Northwest Georgia Oncology Centers Marietta	Marietta	Georgia
United States	Ascension Sacred Heart	Pensacola	Florida
United States	Northwest Medical Specialties	Puyallup	Washington
United States	Scripps Health	San Diego	California
United States	University of Washington	Seattle	Washington
United States	Medical Oncology Associates	Spokane	Washington
United States	Oncology Hematology Associates	Springfield	Missouri
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Cotton Oneil Cancer Center	Topeka	Kansas
United States	Northeast Texas Cancer and Research Institute	Tyler	Texas
United States	Prairie Lakes Healthcare System	Watertown	South Dakota
United States	Clinical Research Alliance, Inc	Westbury	New York
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Mainline Health Lankenau Institute For Medical Research	Wynnewood	Pennsylvania
United States	Cancer Care Associates of York	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  China,  Czechia,  France,  Georgia,  Ireland,  Israel,  Italy,  Korea, Republic of,  Poland,  Portugal,  Puerto Rico,  Romania,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival As Determined By A Blinded Independent Review Committee (BIRC)		Approximately 78 months
Secondary	Progression-free Survival As Determined By Investigator Assessment		Approximately 87 months
Secondary	Duration Of Response As Determined By BIRC And By Investigator Assessment		Approximately 87 months
Secondary	Overall Response Rate As Determined By BIRC And By Investigator Assessment		Approximately 87 months
Secondary	Complete Response Rate As Determined By BIRC And By Investigator Assessment		Approximately 87 months
Secondary	Time To Response As Determined By BIRC And By Investigator Assessment		Approximately 87 months
Secondary	Time to Next Ant-Lymphoma Treatment		Approximately 87 months
Secondary	Overall Survival		Approximately 87 months
Secondary	Health-related Quality Of Life (HRQoL) Using EORTC QLQ-C30)	HRQ0L assessed by The European Organization For Research On Treatment Of Cancer Quality Of Life Questionnaire-core 30 (EORTC QLQ-C30) consists of 30 questions that are associated with 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and 6 single symptom items ( dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The scores range from 0 to 100 and higher score indicates better quality of life.	Approximately 87 months
Secondary	HRQoL Using European Quality of Life 5 Dimension 5 Level Questionnaire [EQ 5D 5L)	The EQ-5D-5L is comprised of a descriptive module and a visual analogue scale. The EQ-5D-5L descriptive module comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The visual analogue scale records the respondent's self-rated health on a 0 to 100 scale, with 100 labeled "the best health you can imagine" and 0 labeled "the worst health you can imagine. Higher scores indicate better quality of life.	Approximately 87 months
Secondary	HRQoL Using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 [FLymSI 18)	The FLymSI-18 is comprised of 18 questions which cover 4 sub-scales: physical symptoms, emotional symptoms, side effects, and functional well-being. Scores are based on the 5-level Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score. Higher score indicates better quality of life.	Approximately 87 months
Secondary	Number of Participants Experiencing Adverse Events (AEs)		From first dose to 28 days after the last dose of zanubrutinib or lenalidomide, 90 days after the last dose of obinutuzumab or rituximab, or until the date of confirmed disease progression, whichever comes later (Approximately 87 months)