This is a prospective, open-label, single-arm clinical trial evaluating a treatment strategy for previously untreated Mantle Cell Lymphoma (MCL). The study will enroll patients who have not received prior systemic therapy for MCL. All patients will receive the ZGR induction regimen. Risk-adapted maintenance therapy will be applied: non-high-risk patients will receive lenalidomide and zanubrutinib maintenance for 1 and 2 years, respectively; high-risk patients will undergo CAR-T cell therapy followed by the same maintenance regimen. The primary objective is to assess the feasibility and preliminary efficacy of this treatment approach in the first-line setting of MCL.
Age between 18 and 80 years inclusive, both genders are eligible.
Histologically or cytologically confirmed diagnosis of Mantle Cell Lymphoma (MCL), with at least one measurable lesion according to Lugano criteria.
No prior systemic therapy for MCL.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Known central nervous system (CNS) involvement, including brain or meningeal lymphoma.
Congestive heart failure with New York Heart Association (NYHA) Class III or IV cardiac dysfunction.
History of other primary malignancies within the past 3 years, except for non-melanoma skin cancer, localized prostate cancer considered cured, cervical in situ carcinoma, or squamous intraepithelial lesion detected by PAP smear.
Prior treatment with investigational drugs.
Single group
Zanubrutinib
DrugZanubrutinib 160 mg orally twice daily (bid), continuously administered. Used during the induction phase as part of the ZGR regimen for 6 cycles, and continued as maintenance therapy for up to 2 years. For patients not achieving complete response, treatment may be extended beyond 2 years until disease progression or intolerance.
Obinutuzumab
DrugObinutuzumab 1000 mg administered intravenously. Dosing schedule: Days 1, 8, and 15 of Cycle 1; Day 1 of each subsequent cycle starting from Cycle 2. Each cycle is 28 days. Administered as part of the ZGR induction regimen for 6 cycles.
Lenalidomide
DrugLenalidomide 20 mg orally once daily on Days 1-21 of each 28-day cycle. Administered during the induction phase as part of the ZGR regimen for 6 cycles. For maintenance, the dose is reduced to 10 mg once daily on Days 1-21 of each 28-day cycle, for a duration of 1 year.
CAR-T Cell Therapy
Other interventionFor high-risk patients, CAR-T cell therapy is permitted after completion of the induction phase. Initiation of CAR-T therapy is followed by a 2-month recovery period before starting maintenance therapy with zanubrutinib and lenalidomide.
complete response rate (CR)
To assess the complete response rate (CR) at the end of Induction therapy \[Time Frame: up to the end of induction treatment
Overall Response Rate (ORR)
Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after Induction treatment
Duration of Response (DoR)
The length of time between the achievement of criteria for response to treatment (first documented complete or partial response) and the first documented relapse or progression.
Progression-free survival (PFS)
The time from the enrollment of a subject to the occurrence of (in any way) progression of disease or Death for any reason. patients with indeterminate recurrence or Death at the last follow-up, defined as the date of the last Investigation
Overall survival
The time from subject enrollment to Death caused by any reason. for patients lost to follow-up, the time of the lastfollow-up; for patients still alive at the end of study, the date of the end of follow-up.
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