A Study to Investigate the Efficacy of Zanubrutinib Plus Rituximab Compared With Bendamustine Plus Rituximab in Adults With Previously Untreated Mantle Cell Lymphoma Who Are Ineligible for Stem Cell Transplantation

Phase 3

Active, not recruiting

• Conditions: Mantle Cell Lymphoma; Non-Hodgkin Lymphoma
• Interventions: Drug: zanubrutinib; Drug: bendamustine; Drug: rituximab

• Registration Number: NCT04002297
• Lead Sponsor: BeiGene

Brief Summary

This is a randomized study to compare the efficacy and safety of zanubrutinib plus rituximab versus bendamustine plus rituximab in previously untreated participants with mantle cell lymphoma (MCL) who are not eligible for stem cell transplantation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-27
• Study First Submitted QC: 2019-06-27
• Study First Posted: 2019-06-28
• Study Start: 2019-08-20
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2027-03
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

1. ≥70 years of age at the time of informed consent, OR ≥60 and <70 years of age with comorbidities precluding autologous stem cell transplantation
2. Histologically confirmed diagnosis of MCL
3. No prior systemic treatments for MCL
4. Measurable disease by CT/MRI
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Adequate marrow and organ function

Key

Exclusion Criteria

1. Known central nervous system involvement by lymphoma
2. Participants for whom the goal of therapy is tumor debulking prior to stem cell transplant
3. Clinically significant cardiovascular disease
4. History of severe bleeding disorder
5. Unable to swallow capsules or disease significantly affecting gastrointestinal function
6. Active fungal, bacterial and/or viral infection requiring systemic therapy
7. Requires ongoing treatment with a strong CYP3A inhibitor or inducer

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: zanubrutinib plus rituximab	zanubrutinib	Participants will receive zanubrutinib plus rituximab, followed by zanubrutinib monotherapy until Independent Review Committee (IRC)-confirmed disease progression.
Arm A: zanubrutinib plus rituximab	rituximab	Participants will receive zanubrutinib plus rituximab, followed by zanubrutinib monotherapy until Independent Review Committee (IRC)-confirmed disease progression.
Arm B: bendamustine plus rituximab	bendamustine	Participants will receive bendamustine plus rituximab, followed by observation.
Arm B: bendamustine plus rituximab	rituximab	Participants will receive bendamustine plus rituximab, followed by observation.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) determined by independent central review	Up to approximately 7 years	PFS is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
PFS by investigator assessment	Up to approximately 7 years	PFS is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first.
Overall response rate (ORR)	Up to approximately 7 years	ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), determined by independent central review and by investigator assessment.
Time to Response (TTR)	Up to approximately 7 years	TTR, as determined by independent central review and by investigator assessment, and defined as the time from randomization to the first documentation of response.
Rate of complete response (CR) or complete metabolic response	Up to approximately 7 years	Rate of CR or complete metabolic response is defined as the percentage of participants who achieve a CR or complete metabolic response, determined by independent central review and by investigator assessment.
Duration of response (DOR)	Up to approximately 7 years	DOR, as determined by independent central review and by investigator assessment, and defined as the time from the date that response criteria are first met to the date that disease progression is objectively documented or death, whichever occurs first.
Overall survival (OS)	Up to approximately 7 years	OS is defined as the time from randomization to the date of death due to any reason.
Participant-reported outcomes (PROs) as assessed by the European Quality of Life 5-Dimension 5 Level Questionnaire (EQ-5D-5L)	Up to approximately 7 years	EuroQoL-Five Dimensions, Five Levels (EQ-5D-5L) is a generic, self-reported measure of utility that consists of a five-item descriptive system and a visual analogue scale (EQ VAS). The descriptive system involves five health dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Participants may choose from the following response levels: no problems=1; slight problems=2; moderate problems=3; severe problems=4; and unable to/extreme problems=5. Higher values indicate worst health.
PROs as assessed by the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	Up to approximately 7 years	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
Number of participants with adverse events and serious adverse events	Up to approximately 7 years	Number of participants with adverse events and serious adverse events, including laboratory values, vital signs, and physical examination findings.

Trial Locations

Locations (176)

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Icon Cancer Foundation; 🇦🇺 South Brisbane, Queensland, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Quanzhou First Affliated Hospital of Fujian Medical University; 🇨🇳 Quanzhou, Fujian, China

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School; 🇨🇳 Nanjing, Jiangsu, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China

Jilin Cancer Hospital; 🇨🇳 Changchun, Jilin, China

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China

Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No Hospital); 🇨🇳 Ningbo, Zhejiang, China

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