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

• ClinicalTrials.gov Identifier: NCT05100862
• Recruitment Status: Recruiting
• First Posted: October 29, 2021
• Last Update Posted: April 24, 2024
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: September 27, 2021
• First Posted Date: October 29, 2021
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: March 10, 2022
• Estimated Primary Completion Date: July 2028 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 12, 2024): Progression-free Survival As Determined By A Blinded Independent Review Committee (BIRC) [ Time Frame: Approximately 78 months ]
• Original Primary Outcome Measures (submitted: October 21, 2021): Progression-free Survival As Determined By An Independent Review Committee [ Time Frame: Approximately 73 months ]

Current Secondary Outcome Measures (submitted: March 12, 2024)

• Progression-free Survival As Determined By Investigator Assessment [ Time Frame: Approximately 87 months ]
• Duration Of Response As Determined By BIRC And By Investigator Assessment [ Time Frame: Approximately 87 months ]
• Overall Response Rate As Determined By BIRC And By Investigator Assessment [ Time Frame: Approximately 87 months ]
• Complete Response Rate As Determined By BIRC And By Investigator Assessment [ Time Frame: Approximately 87 months ]
• Time To Response As Determined By BIRC And By Investigator Assessment [ Time Frame: Approximately 87 months ]
• Time to Next Ant-Lymphoma Treatment [ Time Frame: Approximately 87 months ]
• Overall Survival [ Time Frame: Approximately 87 months ]
• Health-related Quality Of Life (HRQoL) Using EORTC QLQ-C30) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) ]

Original Secondary Outcome Measures (submitted: October 21, 2021)

• Progression-free Survival As Determined By Investigator Assessment [ Time Frame: Approximately 73 months ]
• Progression-free Survival As Determined By Independent Review Committee (CT-based Lugano Criteria) [ Time Frame: Approximately 73 months ]
• Event-free Survival As Determined By An Independent Review Committee (CT-based Lugano Criteria) and By Investigator Assessment [ Time Frame: Approximately 73 months ]
• Duration Of Response As Determined By An Independent Review Committee And By Investigator Assessment . [ Time Frame: Approximately 73 months ]
• Overall Response Rate As Determined By An Independent Review Committee And By Investigator Assessment [ Time Frame: Approximately 73 months ]
• Complete Response Rate As Determined By An Independent Review Committee And By Investigator Assessment [ Time Frame: Approximately 73 months ]
• Time To Response As Determined By An Independent Review Committee And By Investigator Assessment [ Time Frame: Approximately 73 months ]
• Overall Survival [ Time Frame: Approximately 73 months ]
• Health-related Quality Of Life (HRQoL) [ Time Frame: Approximately 73 months ]
  assessed by The European Organization For Research On Treatment Of Cancer Quality Of Life Questionnaire-core 30 (EORTC QLQ-C30)
• Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: From first dose to 30 days after the last dose of zanubrutinib or lenalidomide, 90 days after the last dose of rituximab, or until the date of confirmed disease progression, whichever comes later ]
• Event-free Survival As Determined By An Independent Review Committee [ Time Frame: Approximately 73 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Zanubrutinib Plus Anti-CD20 Versus Lenalidomide Plus Rituximab in Participants With Relapsed/Refractory Follicular or Marginal Zone Lymphoma
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Relapsed/Refractory Follicular Lymphoma
• Marginal Zone 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.
  Other Names:

  • BGB-3111
  • Brukinsa
• Drug: 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.
  Other Names:

  • Rituxan
  • MabThera
  • Ruxience
  • Truxima
• Drug: 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.
  Other Name: Revlimid
• Drug: 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.

Study Arms

• Experimental: Follicular Lymphoma Arm A: Zanubrutinib plus Obinutuzumab
  Participants 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.
  Interventions:

  • Drug: Zanubrutinib
  • Drug: Obinutuzumab
• Active Comparator: Follicular Lymphoma Arm B: Lenalidomide plus Rituximab
  Participants will receive lenalidomide and rituximab.
  Interventions:

  • Drug: Rituximab
  • Drug: Lenalidomide
• Experimental: Marginal Zone Lymphoma Arm C: Zanubrutinib plus Rituximab
  Participants 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.
  Interventions:

  • Drug: Zanubrutinib
  • Drug: Rituximab
• Active Comparator: Marginal Zone Lymphoma Arm D: Lenalidomide plus Rituximab
  Participants will receive lenalidomide and rituximab.
  Interventions:

  • Drug: Rituximab
  • Drug: Lenalidomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2022): 750
• Original Estimated Enrollment (submitted: October 21, 2021): 372
• Estimated Study Completion Date: June 2030
• Estimated Primary Completion Date: July 2028 (Final data collection date for primary outcome measure)

Eligibility 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

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Director BeiGene; 1-877-828-5568; clinicaltrials@beigene.com

• Listed Location Countries: Argentina, Australia, Austria, Brazil, China, Czechia, France, Ireland, Israel, Italy, Korea, Republic of, Puerto Rico, Romania, Spain, United Kingdom, United States
• Removed Location Countries: Belgium, Bulgaria, Canada, Georgia, Germany, Greece, Netherlands, Poland, Portugal, South Africa, Switzerland, Turkey

Administrative Information

• NCT Number: NCT05100862
• Other Study ID Numbers: BGB-3111-308; CTR20232545 ( Registry Identifier: ChinaDrugTrials ); 2022-502548-12-00 ( Registry Identifier: EU CTIS )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; BeiGene
• Principal Investigator: Study Director; BeiGene

• PRS Account: BeiGene
• Verification Date: April 2024