Zanubrutinib-based Induction and Maintenance Therapy in Young and Fit Patients With Untreated Mantle Cell Lymphoma

Inclusion Criteria:

1. 1. Histologically confirmed diagnosis of MCL according to WHO classification
2. Previously untreated MCL
3. Suitable for high-dose treatment including high-dose Ara-C
4. Age ≥ 18 years and ≤ 65 years
5. Stage II-IV (Ann Arbor)
6. Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI).Measurable disease was defined as at least 1 lymph node > 1.5 cm in longest diameterand measurable in 2 perpendicular dimensions; in case of bone marrow infiltrationonly, bone marrow aspiration and biopsy are mandatory for all staging evaluations
7. ECOG performance status ≤ 2
8. The following laboratory values at screening (unless related to MCL):

• Absolute neutrophil count (ANC) ≥ 1×10⁹/L
• Platelets ≥ 75×10⁹/L (platelets ≥ 50×10⁹/L with bone marrow involvement)
• Transaminases (AST and ALT) ≤ 3 × upper limit of normal (ULN)
• Total bilirubin ≤ 2 × ULN (unless documented Gilbert's syndrome)
• Calculated creatinine clearance ≥ 30 mL/min

9. International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 xupper limit of normal. If a factor inhibitor was present with prolongation of theinternational normalized ratio or activated partial thromboplastin time.
10. Sexually active men and women of child-bearing potential must agree to use highlyeffective contraceptives (eg, condoms, implants, injectables, combined oralcontraceptives, intrauterine devices, sexual abstinence, or sterilized partner) whileon study; this should be maintained for 90 days after the last dose of study drug
11. Life expectancy of> 3 months
12. Written informed consent form according to GCP and national regulations

Exclusion Criteria:

1. Known CNS involvement of MCL
2. Major surgery within 4 weeks of screening
3. Prior hematopoietic stem cell transplantation
4. Concomitant or previous malignancies within the last 2 years other than basal cellskin cancer or in situ uterine cervix cancer
5. Clinically significant cardiovascular disease such as uncontrolled arrhythmias andhypertension , congestive heart failure, or myocardial infarction within 6 months ofScreening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined bythe New York Heart Association Functional Classification or LVEF below 50%（AHA，2016）
6. QTcF > 450 msec or other significant electrocardiogram (ECG) abnormalities includingsecond-degree atrioventricular block Type II, or third-degree atrioventricular block
7. Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactionsto the compound of zanubrutinib itself or to the excipients in its formulation)
8. Requires treatment with strong CYP3A inhibitors or strong CYP3A inducers
9. Unable to swallow capsules or disease significantly affecting gastrointestinalfunction such as malabsorption syndrome, resection of the stomach or small bowel,bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial orcomplete bowel obstruction
10. Patients with unresolved hepatitis B or C infection or known HIV positive infection
11. Active infection including infections requiring oral or intravenous antimicrobialtherapy
12. Any life-threatening illness, medical condition, or organ system dysfunction that, inthe investigator's opinion, could have compromised the patient's safety, or put thestudy at risk
13. History of stroke or intracranial hemorrhage within 6 months before first dose ofstudy drug
14. Pregnancy or lactation
15. Participation in another clinical trial within 30 days before enrollment in this study
16. poor compliance