NCT05976763|RecruitingPhase 3

Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma

A Randomized Phase 3 Trial of Continuous vs. Intermittent Maintenance Therapy With Zanubrutinib as Upfront Treatment in Older Patients With Mantle Cell Lymphoma

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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2 other identifiers

A052101NCI-2023-03577

Study Type

interventional

Target

421

Locations

1 country

Sites

231

Timeline

RegisteredAug 2023

StartedOct 2023

CompletionAug 2038

Brief Summary

This phase III trial tests whether continuous or intermittent zanubrutinib after achieving a complete remission (CR) with rituximab works in older adult patients with mantle cell lymphoma (MCL) who have not received treatment in the past (previously untreated). Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. When zanubrutinib is used in MCL, the current standard of care is to continue administering the drug indefinitely until disease progression. This continuous treatment comes with clinical as well as financial toxicity, which could be especially detrimental in older patients. For patients who achieve a CR after initial zanubrutinib plus rituximab therapy, it may be safe and equally effective to stop treatment and restart zanubrutinib upon disease progression rather than continuing indefinitely in previously untreated older adult patients with MCL.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

421

participants targeted

Target at P50-P75 for phase_3

Timeline

150mo left

Started Oct 2023

Longer than P75 for phase_3

Geographic Reach

1 country

231 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

14.9 years study duration

Study Progress17%

Oct 2023Aug 2038

First Submitted

Initial submission to the registry

July 26, 2023

Completed

9 days until next milestone

First Posted

Study publicly available on registry

August 4, 2023

Completed

3 months until next milestone

Study Start

First participant enrolled

October 20, 2023

Completed

14.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2038

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2038

Last Updated

March 4, 2026

Status Verified

March 1, 2026

Enrollment Period

14.9 years

First QC Date

July 26, 2023

Last Update Submit

March 2, 2026

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

Progression-free survival (PFS) 1 (Arm A)
Hazard ratios on the treatment effect will be estimated using a stratified cox proportional hazards model, stratified on age and mantle cell lymphoma (MCL) International Prognostic Index (IPI) score. The primary analysis for non-inferiority will be based on an intent-to-treat (ITT) analysis and will include all randomized patients in the analyses, regardless of eligibility or treatment status. Sensitivity analyses will also be done in an ancillary manner to evaluate and compare our endpoints using a modified ITT approach, and exclude from the analysis those classified as ineligible as well as those who withdraw right after randomization prior to any treatment/observation monitoring.
Time from randomization until the earlier of first progression or death from any cause, assessed up to 10 years
Progression-free survival (PFS) 2 (Arm B)
Hazard ratios on the treatment effect will be estimated using a stratified cox proportional hazards model, stratified on age and MCL IPI score. The primary analysis for non-inferiority will be based on an ITT analysis and will include all randomized patients in the analyses, regardless of eligibility or treatment status. Sensitivity analyses will also be done in an ancillary manner to evaluate and compare our endpoints using a modified ITT approach, and exclude from the analysis those classified as ineligible as well as those who withdraw right after randomization prior to any treatment/observation monitoring.
Time from randomization until the earlier of second progression or death from any cause, assessed up to 10 years

Secondary Outcomes (6)

Overall survival (OS) (Arms A and B)
Time from randomization until death from any cause, assessed up to 10 years
Incidence of adverse events
Up to 10 years
Overall response rate (ORR, complete + partial remission)
up to 10 years
Complete response rate (CR)
Up to 10 years
Event-free survival (EFS) 1
Time from randomization (Arms A and B) until the earlier of first progression, start of an alternative MCL therapy, or death from any cause, assessed up to 10 years.
+1 more secondary outcomes

Study Arms (3)

Induction therapy (Zanubrutinib, rituximab)

EXPERIMENTAL

Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial.

Drug: ZanubrutinibBiological: RituximabOther: Patient ObservationProcedure: Bone Marrow BiopsyOther: Fludeoxyglucose F-18Procedure: Positron Emission TomographyProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: EsophagogastroduodenoscopyProcedure: ColonoscopyProcedure: Biospecimen CollectionOther: Questionnaire Administration

Arm A (Zanubrutinib)

EXPERIMENTAL

Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.

Drug: ZanubrutinibOther: Patient ObservationProcedure: Bone Marrow BiopsyOther: Fludeoxyglucose F-18Procedure: Positron Emission TomographyProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: EsophagogastroduodenoscopyProcedure: ColonoscopyProcedure: Biospecimen CollectionOther: Questionnaire Administration

ARM B (Observation)

ACTIVE COMPARATOR

Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.