A Single-arm, Single-center, Open-label Phase II Study of Zanubrutinib Combined With R-CHOP/R-DHAP in Newly Diagnosed Mantle CellLymphoma Patients

Korábbi kezelés

• Major surgery within 4 weeks of screening
• Requires treatment with strong CYP3A inhibitors or strong CYP3A inducers
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
• Participation in another clinical trial within 30 days before enrollment in this study

Más betegség

• Concomitant or previous malignancies within the last 2 years other than basal cell skin cancer or in situ uterine cervix cancer
• Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of zanubrutinib itself or to the excipients in its formulation)
• Unable to swallow capsules or 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
• Active infection including infections requiring oral or intravenous antimicrobial therapy
• Patients with unresolved hepatitis B or C infection or known HIV positive infection
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk

Laborértékek

• Clinically significant cardiovascular disease such as uncontrolled arrhythmias and hypertension , congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below 50%（AHA，2016）

Egyéb

• Known CNS involvement of MCL, Leukemic non-lymphonodular mantle cell lymphoma was excluded.
• QTcF > 450 msec or other significant electrocardiogram (ECG) abnormalities including second-degree atrioventricular block Type II, or third-degree atrioventricular block
• Pregnancy or lactation
• poor compliance

• Histologically confirmed diagnosis of MCL according to WHO classification;
• Previously untreated MCL.
• Age ≥ 18 and ≤ 70 years old.
• ECOG, 0~2.
• Suitable for high-dose treatment including high-dose Ara-C.
• Stage II-IV (Ann Arbor).
• 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 diameter and measurable in 2 perpendicular dimensions; in case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations.
• The following laboratory tests during the screening period (unless related to MCL disease)
• 1) Neutrophils ≥1×109/L within 7 days prior to study entry, and no growth factor support therapy.
• 2) Platelets ≥75×109/L within 7 days prior to study entry without growth factor support or blood transfusion.
• 3) Hemoglobin ≥75g/L shall not be transfused within 7 days before the test. If bone marrow is involved, neutrophils ≥0.75×109/L, platelets ≥50×109/L, hemoglobin ≥50g/L)
• 4) Creatinine clearance ≥30ml/min
• 5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× upper limit of normal (ULN).
• International Standardized ratio (INR) ≤1.5 and activated partial prothrombin kinase time (APTT) ≤1.5×ULN. If there is a clotting factor inhibitor that causes an elevated INR or prolonged APTT, it is up to the investigator to decide whether to enroll the patient.
• Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug
• Life expectancy > 3 months.
• Written informed consent form according to GCP and national regulations.