Study Comparing Zanubrutinib + Rituximab Versus Bendamustine + Rituximab in Participants With Untreated Mantle Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT04002297
• Recruitment Status: Recruiting
• First Posted: June 28, 2019
• Last Update Posted: December 1, 2021
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: June 27, 2019
• First Posted Date: June 28, 2019
• Last Update Posted Date: December 1, 2021
• Actual Study Start Date: August 21, 2019
• Estimated Primary Completion Date: March 2027 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 27, 2019): Progression-free survival (PFS) determined by independent central review [ Time Frame: Up to 7 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 20, 2020)

• PFS by investigator [ Time Frame: Up to 7 years ]
• Overall response rate (ORR) [ Time Frame: Up to 7 years ]
• Duration of response (DOR) [ Time Frame: Up to 7 years ]
• Overall survival (OS) [ Time Frame: Up to 7 years ]
• Participant-reported outcomes (PROs) as assessed by the EQ-5D-5L questionnaire [ Time Frame: Up to 7 years ]
• PROs as assessed by the EORTC QLQ-C30 questionnaire [ Time Frame: Up to 7 years ]
• Occurrence and severity of treatment-emergent adverse events (safety and tolerability) [ Time Frame: Up to 7 years ]

Original Secondary Outcome Measures (submitted: June 27, 2019)

• PFS by investigator [ Time Frame: Up to 7 years ]
• Overall response rate (ORR) [ Time Frame: Up to 7 years ]
• Duration of response (DOR) [ Time Frame: Up to 7 years ]
• Overall survival (OS) [ Time Frame: Up to 7 years ]
• Patient-reported outcomes (PROs) as measured by the EQ-5D-5L questionnaire [ Time Frame: Up to 7 years ]
• PROs as measured by the EORTC QLQ-C30 questionnaire [ Time Frame: Up to 7 years ]
• Occurrence and severity of treatment-emergent adverse events (safety and tolerability) [ Time Frame: Up to 7 years ]

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

Descriptive Information

• Brief Title: Study Comparing Zanubrutinib + Rituximab Versus Bendamustine + Rituximab in Participants With Untreated Mantle Cell Lymphoma
• Official Title: A Phase 3 Randomized, Open-Label, Multicenter Study Comparing Zanubrutinib (BGB-3111) Plus Rituximab Versus Bendamustine Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma Who Are Ineligible for Stem Cell Transplantation
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Mantle Cell Lymphoma; Non-Hodgkin Lymphoma

Intervention

• Drug: zanubrutinib
  Administered as two 80 mg capsules by mouth twice a day
  Other Names:

  • BGB-3111
  • Brukinsa
• Drug: bendamustine
  Administered intravenously at a dose of 90 mg/m2/day on Days 1 and 2 of Cycles 1 to 6
• Drug: rituximab
  Administered intravenously at a dose of 375 mg/m2 on Day 1 of Cycles 1 to 6

Study Arms

• Experimental: zanubrutinib plus rituximab
  Interventions:

  • Drug: zanubrutinib
  • Drug: rituximab
• Active Comparator: bendamustine plus rituximab
  Interventions:

  • Drug: bendamustine
  • Drug: rituximab

• Publications *: Dreyling M, Tam CS, Wang M, Smith SD, Ladetto M, Huang H, Novotny W, Co M, Romano A, Holmgren E, Huang J, Gouill SL. A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Future Oncol. 2021 Jan;17(3):255-262. doi: 10.2217/fon-2020-0794. Epub 2020 Sep 28.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 27, 2019): 500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2027
• Estimated Primary Completion Date: March 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. ≥ 70 years of age at the time of informed consent, OR 65-69 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, Austria, Belgium, China, France, Germany, Ireland, Italy, Japan, Lithuania, New Zealand, Poland, Spain, Taiwan, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04002297
• Other Study ID Numbers: BGB-3111-306; 2019-000413-36 ( EudraCT Number )
• 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

• Responsible Party: BeiGene
• Study Sponsor: BeiGene
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: November 2021