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

Phase 3
Recruiting
Conditions
Relapsed/Refractory Follicular Lymphoma
Marginal Zone Lymphoma
Interventions
Registration Number
NCT05100862
Lead Sponsor
BeiGene
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

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
780
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Follicular Lymphoma Arm A: Zanubrutinib plus ObinutuzumabZanubrutinibParticipants will receive zanubrutinib and Obinutuzumab. Following the completion of the combination treatment, participants will continue receiving zanubrutinib monotherapy until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first.
Follicular Lymphoma Arm A: Zanubrutinib plus ObinutuzumabObinutuzumabParticipants will receive zanubrutinib and Obinutuzumab. Following the completion of the combination treatment, participants will continue receiving zanubrutinib monotherapy until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first.
Follicular Lymphoma Arm B: Lenalidomide plus RituximabRituximabParticipants will receive lenalidomide and rituximab.
Marginal Zone Lymphoma Arm C: Zanubrutinib plus RituximabZanubrutinibParticipants will receive zanubrutinib and rituximab. Following the completion of the combination treatment, participants will continue receiving zanubrutinib monotherapy until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first.
Follicular Lymphoma Arm B: Lenalidomide plus RituximabLenalidomideParticipants will receive lenalidomide and rituximab.
Marginal Zone Lymphoma Arm C: Zanubrutinib plus RituximabRituximabParticipants will receive zanubrutinib and rituximab. Following the completion of the combination treatment, participants will continue receiving zanubrutinib monotherapy until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first.
Marginal Zone Lymphoma Arm D: Lenalidomide plus RituximabRituximabParticipants will receive lenalidomide and rituximab.
Marginal Zone Lymphoma Arm D: Lenalidomide plus RituximabLenalidomideParticipants will receive lenalidomide and rituximab.
Primary Outcome Measures
NameTimeMethod
Progression-free Survival As Determined By A Blinded Independent Review Committee (BIRC)Approximately 78 months
Secondary Outcome Measures
NameTimeMethod
Time to Next Ant-Lymphoma TreatmentApproximately 87 months
Overall SurvivalApproximately 87 months
Progression-free Survival As Determined By Investigator AssessmentApproximately 87 months
Overall Response Rate As Determined By BIRC And By Investigator AssessmentApproximately 87 months
Complete Response Rate As Determined By BIRC And By Investigator AssessmentApproximately 87 months
Time To Response As Determined By BIRC And By Investigator AssessmentApproximately 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.

Duration Of Response As Determined By BIRC And By Investigator AssessmentApproximately 87 months
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)

Trial Locations

Locations (289)

Ucsf Fresno University of California San Francisco Fresno

🇺🇸

Fresno, California, United States

Kaiser Permanente Southern California

🇺🇸

Irvine, California, 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

UCLA Hematologyoncology

🇺🇸

Los Angeles, California, United States

Scripps Health

🇺🇸

San Diego, California, United States

Sharp Healthcare Sharp Memorial Hospital

🇺🇸

San Diego, California, United States

Baptist Md Anderson Cancer Center

🇺🇸

Jacksonville, Florida, United States

Memorial Cancer Institute, Memorial Healthcare System

🇺🇸

Pembroke Pines, Florida, United States

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Ucsf Fresno University of California San Francisco Fresno
🇺🇸Fresno, California, United States
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