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

Recruiting now · Phase 3

Conditions studied: Mantle Cell Lymphoma

In brief

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.

Key facts

Study ID

NCT05976763

Run by

Alliance for Clinical Trials in Oncology

People needed

421

Starts

2023-10-20

Expected to finish

2038-08-31

Last updated by the study team

2026-08-06

Who can join

Age: 60 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• • Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or 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). Patients with cyclin D1 and/or t(11;14) negative mantle cell lymphoma with an expression profile suggesting a diagnosis of mantle cell lymphoma [MCL] such as SOX11 expression are also eligible
• Any stage allowed (stage I-IV)
• Patient must have at least one objective measurable disease parameter by PET or CT. Measurable disease in the liver is required if the liver is the only site of lymphoma OR bone marrow involvement by MCL
• Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days prior to registration
• No prior systemic treatment for mantle cell lymphoma
• No prior radiation treatment for stage I MCL
• No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody
• No prior stem cell transplant
• Age >= 70 years OR age >= 60 to < 70 years with comorbidities precluding autologous stem cell transplantation (autoSCT) including at least one of the following: a) cardiac ejection fraction (EF) <= 45%, b) diffusing capacity for carbon monoxide <= 60% predicted; c) creatinine clearance < 70 but >= 30ml/minute (min); d) Eastern Cooperative Oncology Group (ECOG) performance status of 2, which poses an unacceptable risk of toxicity for high-dose therapy and stem cell transplantation; or e) Cumulative Illness Rating Scales (CIRS) total score > 6
• ECOG Performance Status 0-2
• 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 upper limit of normal (ULN) (unless documented Gilbert's syndrome)
• Aspartate transferase (AST) / alanine transaminase (ALT) =< 3 x ULN
• Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy
• 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
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• No active Hepatitis B or Hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Where it is running

• Augusta University Medical Center — Augusta, Georgia, United States (enrolling)
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (enrolling)
• Tower Cancer Research Foundation — Beverly Hills, California, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center at Glastonbury — Glastonbury, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center at Greenwich — Greenwich, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center at Saint Francis — Hartford, Connecticut, United States (enrolling)
• Yale University — New Haven, Connecticut, United States (enrolling)
• Yale-New Haven Hospital North Haven Medical Center — North Haven, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center at Long Ridge — Stamford, Connecticut, United States (enrolling)
• Smilow Cancer Hospital-Torrington Care Center — Torrington, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States (enrolling)
• Smilow Cancer Hospital-Waterbury Care Center — Waterbury, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States (enrolling)
• Helen F Graham Cancer Center — Newark, Delaware, United States (enrolling)
• Medical Oncology Hematology Consultants PA — Newark, Delaware, United States (enrolling)
• Phoebe Putney Memorial Hospital — Albany, Georgia, United States (enrolling)
• Grady Health System — Atlanta, Georgia, United States (enrolling)
• Emory University Hospital Midtown — Atlanta, Georgia, United States (enrolling)
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States (enrolling)
• Emory Saint Joseph's Hospital — Atlanta, Georgia, United States (enrolling)
• Emory Johns Creek Hospital — Johns Creek, Georgia, United States (enrolling)

Full record on ClinicalTrials.gov

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