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Official Title
A Randomized Phase 3 Trial of Continuous vs. Intermittent Maintenance Therapy With Zanubrutinib as Upfront Treatment in Older Patients With Mantle Cell Lymphoma
Phase
Phase 3
Sponsor
Alliance for Clinical Trials in Oncology
Enrollment
421
Timeline
Oct 2023 → Aug 2038
About This Study
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.
Eligibility Criteria
Inclusion Criteria
- 1• Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) as confirmed by the enrolling center
- 2Any stage allowed (stage I-IV)
- 3Presence of measurable disease, defined as \>= 1 nodal lesion that is \> 1.5 cm in longest diameter or \>= 1 extranodal lesion that is \> 1 cm in longest diameter
- 4Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days
- 5No prior systemic treatment for mantle cell lymphoma
- 6No prior radiation treatment for stage I MCL
- 7No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody
- 8No prior stem cell transplant
- 9Age \>= 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
- 10ECOG Performance Status 0-2
- 11Absolute neutrophil count (ANC) \>= 750/mm\^3 (without growth factor support within 7 days)
- 12Platelet count \>= 75,000/mm\^3 (or \>= 50,000/mm\^3 for patients with bone marrow involvement of lymphoma) without growth factor support or transfusion within 7 days
- 13Creatinine 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
- 14Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
- 15Aspartate transferase (AST) / alanine transaminase (ALT) =\< 3 x ULN
- 16Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy
- 17No clinically significant cardiovascular disease including the following
- 18Unstable angina within 3 months before registration
- 19New York Heart Association class III or IV congestive heart failure
- 20History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- 21QT correction formula (QTcF) \> 480 msecs based on Fredericia's formula
- 22History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
- 23Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- 24No 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
- 25Patients 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
- 26No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- 27No history of stroke or intracranial hemorrhage within 6 months prior to registration
- 28No disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Patient must be able to swallow pills
- 29Potential trial participants should have recovered from major surgery
- 30No vaccination with a live vaccine within 35 days prior to registration
- 31No hypersensitivity to zanubrutinib or rituximab or any of the other ingredients of the study drugs
- 32Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
- 33Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
- 34Avoid use of moderate CYP3A4 inhibitors, PGP inhibitors, and moderate CYP3A4 inducers
- 35Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional
Locations
228 sites participating in this study
Emory University Hospital Midtown
Atlanta, Georgia 30308
Jonathon B. Cohen
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
Jonathon B. Cohen
Emory Saint Joseph's Hospital
Atlanta, Georgia 30342
Jonathon B. Cohen
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →