Clinical trial NCT03332017: A Study Comparing Obinutuzumab and BGB-3111 Versus Obinutuzumab Alone in Treating R/R Follicular Lymphoma
Official title: An International, Phase 2, Open-Label, Randomized Study of BGB-3111 Combined With Obinutuzumab Compared With Obinutuzumab Monotherapy in Relapsed/ Refractory Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed/Refractory Follicular Non-Hodgkin Lymphoma
Keywords: Relapsed/Refractory Follicular non-Hodgkin Lymphoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 217
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: he purpose of the study is to evaluate the efficacy, safety, and tolerability BGB-3111 plus obinutuzumab versus obinutuzumab alone in participants with relapsed/refractory non-Hodgkin follicular lymphoma.


Eligibility criteria: Key Inclusion Criteria:

1. Histologically confirmed diagnosis of B-cell follicular lymphoma
2. ≥2 prior systemic treatments for follicular lymphoma.
3. Previously received an anti-CD20 antibody and an appropriate alkylator-based combination therapy.
4. Disease progression after completion of most recent therapy or refractory disease.
5. Presence of measurable disease.
6. Availability of archival tissue confirming diagnosis.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
8. Adequate renal and hepatic function.

Key Exclusion Criteria:

1. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor.
2. Known central nervous system involvement by leukemia or lymphoma.
3. Evidence of transformation from follicular lymphoma to other aggressive histology.
4. Allogeneic hematopoietic stem cell transplantation within 12 months of enrollment
5. Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix of breast, or localized Gleason score 6 prostate cancer.
6. Clinically significant cardiovascular disease.
7. Major surgery ≤ 4 weeks prior to start of study treatment.
8. Active fungal, bacterial or viral infection requiring systemic treatment.
9. History of severe bleeding disorder.

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

Primary outcomes:
measure: Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment
timeFrame: Through primary analysis data cut-off date of 08OCT2021 (up to approximately 3 years and 11 months)
Secondary outcomes:
measure: Overall Response Rate (ORR) as Assessed by the Investigator
timeFrame: Up to approximately 7 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 7 years
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 7 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 7 years
measure: Complete Response Rate
timeFrame: Up to approximately 7 years
measure: Complete Metabolic Response Rate
timeFrame: Up to approximately 7 years
measure: Time to Response (TTR)
timeFrame: Up to approximately 7 years
measure: Health-Related Quality of Life (HRQOL) as Assessed by The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Up to approximately 7 years
measure: Health-Related Quality of Life (HRQOL) as Assessed by The 5-level EQ-5D Version (EQ-5D-5L)
timeFrame: Up to approximately 7 years
measure: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 7 years
measure: Apparent Clearance (CL/F) of Zanubrutinib
timeFrame: Day 1 Cycle 1 and Day 2 Cycle 2: Predose
measure: Area Under the Curve From 0 to 12 Hours Post Dose (AUC0-12)
timeFrame: Day 1 Cycle 1 and Day 2 Cycle 2: Pre-dose
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Illinois At Chicago
state: Illinois
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital Sydney
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Icon Cancer Centre Wesley
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Foundation
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncological Dispensary
city: Minsk
country: Belarus
facility: Nn Alexandrov National Cancer Centre of Belarus
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Dispensary
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment Dr Georgi Stranski
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Mhat Tokuda Ead
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment Saint Ivan Rilski
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment Alexandrovska
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Opava
country: Czechia
facility: Slezska Nemocnice V Opave
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Amiens Cedex
country: France
facility: Centre Hospitalier Universitaire Damiens Hopital Sud
city: Bordeaux
country: France
facility: Centre de Lutte Contre Le Cancer Institut Bergonie
city: Dunkerque
country: France
facility: Centre Hospitalier de Dunkerque
city: Esseylesnancy
country: France
facility: Clinique Louis Pasteur
city: Paris
country: France
facility: Necker University Hospital
city: Pessac
country: France
facility: Chu Bordeaux Hopital Haut Leveque
city: PierreBenite
country: France
facility: Chu Hopital Lyon Sud
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard
city: Rouen Cedex
country: France
facility: Centre Henri Becquerel
city: Augsburg
country: Germany
facility: Klinikum Augsburg, Ii Medizinische Klinik
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Di Bari
city: Bologna
country: Italy
facility: Policlinico Sorsola Malpighi, Aou Di Bologna
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria Di Parma
city: Ravenna
country: Italy
facility: Unita Di Ematologia, Dipartimento Di Ematologia Ed Oncologia
city: Varese
country: Italy
facility: Ospedale Di Circolo E Fondazione Macchi
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Daegu Gwang'yeogsi
city: Seongnamsi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne Sc
city: Lodz
country: Poland
facility: Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej
city: Opole
country: Poland
facility: Szpital Wojewodzki W Opolu
city: Sochi
country: Russian Federation
facility: State Healthcare Institution Oncologic Dispensary No Health Department of Krasnodar Region
state: Krasnodarskiy Kray
city: Moscow
country: Russian Federation
facility: N N Blokhin Russian Cancer Research Center Konstantin Laktionov
state: Moskva
city: Yekaterinburg
country: Russian Federation
facility: Central City Hospital
state: Sverdlovskaya Oblast'
city: Tula
country: Russian Federation
facility: Tula Area Clinical Hospital
state: Tul'skaya Oblast'
city: Barcelona
country: Spain
facility: Institut Catala Doncologia
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta Del Mar
city: Madrid
country: Spain
facility: Md Anderson Cancer Center Madrid Spain
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario de Octubre
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital West Campus
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth and Christchurch Hospitals Nhs Foundation
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals Nhs Trust
city: London
country: United Kingdom
facility: Barts Health Nhs Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals Nhs Foundation Trust
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Trotman J, Folwer N, Auer R, Flowers C, Reed W, Stern JC, Huang J, Zinzani PL. Phase 2 Obinutuzumab Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Follicular Lymphoma (R/R FL). American Society of Clinical Oncology, 2018.
citation: Fowler N, Trotman J, Auer R, Flowers C, Reed W, Marimpietri C, Huang J, Zinzani PL.Randomized phase 2 zanubrutinib (BGB-3111) + obinutuzumab (obi) vs obi monotherapy in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL). American Society of Clinical Oncology. 2019
citation: Fowler NH, Trotman J, Auer R, Flowers CR, Reed WF, Ivanova E, Huang J, Zinzani PL.Randomized Phase 2 Zanubrutinib (BGB-3111) + Obinutuzumab vs Obinutuzumab Monotherapy in Patients with Relapsed/Refractory Follicular Lymphoma (R/R FL). American Society of Hematology. 2019