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OncoMatch/Clinical Trials/NCT05976763

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

Is NCT05976763 recruiting? Yes, currently enrolling (Sep 2026). This Phase 3 trial studies multiple treatments including Rituximab and Zanubrutinib for mantle cell lymphoma.

Phase 3RecruitingAlliance for Clinical Trials in OncologyNCT05976763Data as of Sep 2026

Treatment: Zanubrutinib · RituximabThis 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.

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Extracted eligibility criteria

Treatments studied

Immunotherapy

Rituximab

Targeted therapy

Zanubrutinib

Cancer type

Non-Hodgkin Lymphoma

Biomarker criteria

Required: CCND1 rearrangement

evidence of CCND1 rearrangement or t(11;14)(q13;q32) as confirmed by the enrolling center (such as by fluorescence in situ hybridization [FISH], polymerase chain reaction [PCR]/sequencing, karyotype)

Required: CCND1 expression

cyclin D1 (BCL1) expression by immunohistochemical stains

Required: SOX11 expression

SOX11 expression

Disease stage

Required: Stage I, II, III, IV

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Demographics

Ages ≥ 60

Prior therapy

No prior treatment (treatment-naive required)
Max 0 prior lines

Cannot have received: systemic therapy for mantle cell lymphoma

No prior systemic treatment for mantle cell lymphoma

Cannot have received: radiation therapy for stage I mantle cell lymphoma

No prior radiation treatment for stage I MCL

Cannot have received: BTK inhibitor

No prior exposure to a BTK inhibitor

Cannot have received: anti-CD20 monoclonal antibody

No prior exposure to an anti-CD20 monoclonal antibody

Cannot have received: stem cell transplant

No prior stem cell transplant

Lab requirements

Blood counts

ANC >= 750/mm^3 (without growth factor support within 7 days); Platelet count >= 75,000/mm^3 (or >= 50,000/mm^3 if thrombocytopenia is due to lymphoma) without growth factor support or transfusion within 7 days

Kidney function

Creatinine clearance >= 30 mL/min determined by Cockcroft-Gault equation, nuclear medicine scan, or 24 hour urine collection

Liver function

Total bilirubin <= 1.5 x ULN (unless documented Gilbert's syndrome); AST/ALT <= 3 x ULN

Cardiac function

No unstable angina within 3 months; No NYHA class III or IV CHF; No clinically significant arrhythmias; QTcF > 480 msec excluded unless pacemaker in place; No Mobitz II second-degree or third-degree heart block without permanent pacemaker

Absolute neutrophil count (ANC) >= 750/mm^3 (without growth factor support within 7 days); Platelet count >= 75,000/mm^3 (or >= 50,000/mm^3 if thrombocytopenia is due to lymphoma) without growth factor support or transfusion within 7 days; Creatinine clearance >= 30 mL/ min determined by either: a) Estimation using the Cockcroft-Gault equation or b) Measurement by nuclear medicine scan or 24 hour urine collection; Total bilirubin <= 1.5 x ULN (unless documented Gilbert's syndrome); AST/ALT <= 3 x ULN; No clinically significant cardiovascular disease including the following: Unstable angina within 3 months before registration; New York Heart Association class III or IV congestive heart failure; History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes); Known QT correction formula (QTcF) > 480 msecs based on Fredericia's formula (unless pacemaker in place); History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • The James Graham Brown Cancer Center at University of Louisville · Louisville, Kentucky
  • UofL Health Medical Center Northeast · Louisville, Kentucky
  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor · Ann Arbor, Michigan
  • McLaren Cancer Institute-Bay City · Bay City, Michigan
  • Trinity Health IHA Medical Group Hematology Oncology - Brighton · Brighton, Michigan

Showing up to 5 US sites.

See all sites on ClinicalTrials.gov →

Frequently asked questions

Is NCT05976763 currently recruiting?

Yes, this trial is currently recruiting patients.

Can patients have received prior systemic therapy?

No. This trial requires treatment-naive patients — prior systemic therapy is an exclusion criterion.

Does this trial require CCND1?

Yes, CCND1 rearrangement is a required biomarker for enrollment.

Does this trial require CCND1?

Yes, CCND1 expression is a required biomarker for enrollment.

Does this trial require SOX11?

Yes, SOX11 expression is a required biomarker for enrollment.

What disease stage is eligible?

Stage I or II or III or IV is required.

Could you qualify for this trial?

Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.

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