Marginal Zone Lymphoma, Relapsed/Refractory Follicular Lymphoma
Conditions
Keywords
Zanubrutinib, BGB-3111, Rituximab, Lenalidomide, Obinutuzumab
Brief 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.
Detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGZanubrutinib
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.
DRUGRituximab
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.
DRUGLenalidomide
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.
DRUGObinutuzumab
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.
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 * Prior treatment with lenalidomide or drug from same class, if without response (partial or complete) or short remission duration (\< 24 months) Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival As Determined By A Blinded Independent Review Committee (BIRC) | Approximately 78 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival As Determined By Investigator Assessment | Approximately 87 months | — |
| Duration Of Response As Determined By BIRC And By Investigator Assessment | Approximately 87 months | — |
| Overall Response Rate As Determined By BIRC And By Investigator Assessment | Approximately 87 months | — |
| Complete Response Rate As Determined By BIRC And By Investigator Assessment | Approximately 87 months | — |
| Time To Response As Determined By BIRC And By Investigator Assessment | Approximately 87 months | — |
| Time to Next Ant-Lymphoma Treatment | Approximately 87 months | — |
| Overall Survival | Approximately 87 months | — |
| Health-related Quality Of Life (HRQoL) Using EORTC QLQ-C30) | Approximately 87 months | 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. |
| HRQoL Using European Quality of Life 5 Dimension 5 Level Questionnaire [EQ 5D 5L) | Approximately 87 months | 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. |
| HRQoL Using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 [FLymSI 18) | Approximately 87 months | 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. |
| 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) | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, France, Georgia, Germany, Greece, Ireland, Israel, Italy, Japan, Poland, Portugal, Puerto Rico, Romania, South Africa, South Korea, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
PRINCIPAL_INVESTIGATORStudy Director
BeOne Medicines
Outcome results
None listed