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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 (MAHOGANY)

Primary Purpose

Relapsed/Refractory Follicular Lymphoma, Marginal Zone Lymphoma

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Zanubrutinib
Rituximab
Lenalidomide
Obinutuzumab
Sponsored by
BeiGene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Follicular Lymphoma focused on measuring Zanubrutinib, BGB-3111, Rituximab, Lenalidomide, Obinutuzumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Histologically confirmed grade 1-3a FL or MZL
  • Previously received ≥ 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.

Sites / Locations

  • Valkyrie Clinical TrialsRecruiting
  • Northwest Georgia Oncology Centers MariettaRecruiting
  • Hattiesburg Hematology and Oncology ClinicRecruiting
  • Clinical Research Alliance, IncRecruiting
  • Gosford HospitalRecruiting
  • St George HospitalRecruiting
  • Port Macquarie Base HospitalRecruiting
  • Westmead HospitalRecruiting
  • Sunshine Coast Hospital and Health ServiceRecruiting
  • Townsville University HospitalRecruiting
  • Monash HealthRecruiting
  • St Vincents Hospital MelbourneRecruiting
  • Austin HealthRecruiting
  • Cabrini Hospital MalvernRecruiting
  • Epworth FreemasonsRecruiting
  • The Alfred HospitalRecruiting
  • Perth Blood InstituteRecruiting
  • La Trobe Regional HospitalRecruiting
  • Inje University Busan Paik HospitalRecruiting
  • Dong A University HospitalRecruiting
  • Pusan National University HospitalRecruiting
  • Seoul National University Bundang HospitalRecruiting
  • Korea University Anam HospitalRecruiting
  • Kyungpook National University Chilgok HospitalRecruiting
  • Gyeongsang National University HospitalRecruiting
  • Chonnam National University Hwasun HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Severance Hospital Yonsei University Health SystemRecruiting
  • Soon Chun Hyang University Hospital SeoulRecruiting
  • Asan Medical CenterRecruiting
  • Samsung Medical CenterRecruiting
  • The Catholic University of Korea, Seoul St Marys HospitalRecruiting
  • Pan American Oncology Trials, LlcRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Follicular Lymphoma Arm A: Zanubrutinib plus Obinutuzumab

Follicular Lymphoma Arm B: Lenalidomide plus Rituximab

Marginal Zone Lymphoma Arm C: Zanubrutinib plus Rituximab

Marginal Zone Lymphoma Arm D: Lenalidomide plus Rituximab

Arm Description

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.

Participants will receive lenalidomide and 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.

Participants will receive lenalidomide and rituximab.

Outcomes

Primary Outcome Measures

Progression-free Survival As Determined By An Independent Review Committee

Secondary Outcome Measures

Progression-free Survival As Determined By Investigator Assessment
Duration Of Response As Determined By An Independent Review Committee And By Investigator Assessment .
Overall Response Rate As Determined By An Independent Review Committee And By Investigator Assessment
Complete Response Rate As Determined By An Independent Review Committee And By Investigator Assessment
Time To Response As Determined By An Independent Review Committee And By Investigator Assessment
Time to Next Ant-Lymphoma Treatment
Overall Survival
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.
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.
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.
Number of Participants Experiencing Adverse Events (AEs)

Full Information

First Posted
September 27, 2021
Last Updated
September 26, 2023
Sponsor
BeiGene
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1. Study Identification

Unique Protocol Identification Number
NCT05100862
Brief Title
A Study of Zanubrutinib Plus Anti-CD20 Versus Lenalidomide Plus Rituximab in Participants With Relapsed/Refractory Follicular or Marginal Zone Lymphoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2022 (Actual)
Primary Completion Date
August 2028 (Anticipated)
Study Completion Date
June 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Follicular Lymphoma, Marginal Zone Lymphoma
Keywords
Zanubrutinib, BGB-3111, Rituximab, Lenalidomide, Obinutuzumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
750 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Follicular Lymphoma Arm A: Zanubrutinib plus Obinutuzumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Follicular Lymphoma Arm B: Lenalidomide plus Rituximab
Arm Type
Active Comparator
Arm Description
Participants will receive lenalidomide and rituximab.
Arm Title
Marginal Zone Lymphoma Arm C: Zanubrutinib plus Rituximab
Arm Type
Experimental
Arm Description
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.
Arm Title
Marginal Zone Lymphoma Arm D: Lenalidomide plus Rituximab
Arm Type
Active Comparator
Arm Description
Participants will receive lenalidomide and rituximab.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111, Brukinsa
Intervention Description
Zanubrutinib will be administered orally as two 80-milligram (mg) capsules twice a day (160 mg twice a day or 320 mg once a day) continuously in repeated 28-day cycles.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, MabThera, Ruxience, Truxima
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide will be administered orally as 20-mg capsules once a day on Days 1 to 21 of each 28-day cycle for a total of 12 cycles.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival As Determined By An Independent Review Committee
Time Frame
Approximately 78 months
Secondary Outcome Measure Information:
Title
Progression-free Survival As Determined By Investigator Assessment
Time Frame
Approximately 87 months
Title
Duration Of Response As Determined By An Independent Review Committee And By Investigator Assessment .
Time Frame
Approximately 87 months
Title
Overall Response Rate As Determined By An Independent Review Committee And By Investigator Assessment
Time Frame
Approximately 87 months
Title
Complete Response Rate As Determined By An Independent Review Committee And By Investigator Assessment
Time Frame
Approximately 87 months
Title
Time To Response As Determined By An Independent Review Committee And By Investigator Assessment
Time Frame
Approximately 87 months
Title
Time to Next Ant-Lymphoma Treatment
Time Frame
Approximately 87 months
Title
Overall Survival
Time Frame
Approximately 87 months
Title
Health-related Quality Of Life (HRQoL) Using EORTC QLQ-C30)
Description
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.
Time Frame
Approximately 87 months
Title
HRQoL Using European Quality of Life 5 Dimension 5 Level Questionnaire [EQ 5D 5L)
Description
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.
Time Frame
Approximately 87 months
Title
HRQoL Using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 [FLymSI 18)
Description
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.
Time Frame
Approximately 87 months
Title
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Histologically confirmed grade 1-3a FL or MZL Previously received ≥ 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director BeiGene
Phone
1-877-828-5568
Email
clinicaltrials@beigene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
BeiGene
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
BeiGene
Official's Role
Principal Investigator
Facility Information:
Facility Name
Valkyrie Clinical Trials
City
Los Angeles
State/Province
California
ZIP/Postal Code
90067
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwest Georgia Oncology Centers Marietta
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Individual Site Status
Recruiting
Facility Name
Hattiesburg Hematology and Oncology Clinic
City
Hattiesburg
State/Province
Mississippi
ZIP/Postal Code
39401
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinical Research Alliance, Inc
City
Westbury
State/Province
New York
ZIP/Postal Code
11590
Country
United States
Individual Site Status
Recruiting
Facility Name
Gosford Hospital
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
2250
Country
Australia
Individual Site Status
Recruiting
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Recruiting
Facility Name
Port Macquarie Base Hospital
City
Port Macquarie
State/Province
New South Wales
ZIP/Postal Code
2444
Country
Australia
Individual Site Status
Recruiting
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Name
Sunshine Coast Hospital and Health Service
City
Birtinya
State/Province
Queensland
ZIP/Postal Code
4575
Country
Australia
Individual Site Status
Recruiting
Facility Name
Townsville University Hospital
City
Douglas
State/Province
Queensland
ZIP/Postal Code
4814
Country
Australia
Individual Site Status
Recruiting
Facility Name
Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
St Vincents Hospital Melbourne
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Individual Site Status
Recruiting
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cabrini Hospital Malvern
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Individual Site Status
Recruiting
Facility Name
Epworth Freemasons
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Individual Site Status
Recruiting
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Perth Blood Institute
City
West Perth
State/Province
Western Australia
ZIP/Postal Code
6005
Country
Australia
Individual Site Status
Recruiting
Facility Name
La Trobe Regional Hospital
City
Melbourne
ZIP/Postal Code
3844
Country
Australia
Individual Site Status
Recruiting
Facility Name
Inje University Busan Paik Hospital
City
Busan
State/Province
Busan Gwang'yeogsi
ZIP/Postal Code
47392
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Dong A University Hospital
City
Busan
State/Province
Busan Gwang'yeogsi
ZIP/Postal Code
49201
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Pusan National University Hospital
City
Busan
State/Province
Busan Gwang'yeogsi
ZIP/Postal Code
49241
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Bundang Hospital
City
Seongnamsi
State/Province
Gyeonggido
ZIP/Postal Code
13620
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Korea University Anam Hospital
City
Seoul
State/Province
Gyeonggido
ZIP/Postal Code
02841
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Kyungpook National University Chilgok Hospital
City
Daegu
State/Province
Gyeongsangbukdo
ZIP/Postal Code
41404
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Gyeongsang National University Hospital
City
Jinjusi
State/Province
Gyeongsangnamdo
ZIP/Postal Code
52727
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Chonnam National University Hwasun Hospital
City
Hwasungun
State/Province
Jeonranamdo
ZIP/Postal Code
58128
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Severance Hospital Yonsei University Health System
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Soon Chun Hyang University Hospital Seoul
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
04401
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Asan Medical Center
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
The Catholic University of Korea, Seoul St Marys Hospital
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
06591
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Pan American Oncology Trials, Llc
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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