Diffuse large B-cell lymphoma
Conditions
Interventions
Experimental group:zanubrutinib and intrathecal chemotherapy
Sponsors
Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: (1) Histopathologically confirmed diffuse large B-cell lymphoma. (2) One of the following risk factors for central nervous system recurrence: ? CNS-IPI score high risk; ? =3 extranodal sites involved; ? Testis, kidney, adrenal gland, mammary gland and uterus involved; ? Intravascular large B-cell lymphoma; ? Primary cutaneous DLBCL leg type. (3) Age of 18 to 65 years old. (4) ECOG score 0-2 points. (5) Bone marrow and organ function meet the following criteria (no blood transfusion within 14 days prior to screening, no G-CSF, no drug intervention) : ? Bone marrow function: neutrophil =1.5×10^9/L, platelet =75×10^9/L, hemoglobin =80g/L; ? Liver function: serum total bilirubin =1.5×ULN (=3.0×ULN, if liver involved), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5×ULN (=5.0×ULN, if liver involved); ? Renal function: serum creatinine =1.5×ULN or estimated creatinine clearance =60ml/min; ? Coagulation function: INR and activated partial thrombin time =1.5 x ULN. (6) Women of reproductive age and fertile men who do not plan to have children during the study period and for 3 months after treatment interruption, and effective contraception must be used during the study period and for 3 months after treatment interruption. Male subjects were prohibited from donating sperm for 3 months from the start of treatment to the end of treatment. (7) Able to receive multiple MRI and lumbar puncture examination. (8) No difficulty in swallowing oral capsules. (9) Expected survival =2 years. (10) Participate in the study voluntarily and sign the informed consent.
Exclusion criteria
Exclusion criteria: (1) Patients with primary entral nervous system diffuse large B-cell lymphoma or central nervous system involvement at diagnosis. (2) Receiving treatment that can cross the blood-brain barrier, including but not limited to: high-dose methotrexate (=1.0g/m2), high-dose cytarabine (=2.0g/m2), lenalidomide, anti-PD-1 antibody, etc. (3) Active bleeding within 4 weeks prior to initial administration, or required anticoagulant therapy such as warfarin/vitamin K antagonists during the study, or the investigator considered that patients exist clotting disorders. (4) Use moderate or strong CYP3A4/5 inhibitors or inducers within 2 weeks prior to initial administration. (5) Uncontrollable or significant cardiovascular disease, including but not limited to: ? Any of the following conditions occur within 6 months prior to initial administration: congestive heart failure (NYHA III or IV), myocardial infarction, unstable angina, or presence of arrhythmia requiring treatment at screening, left ventricular ejection fraction 470ms (female) or 480ms (male), grade II type II atrioventricular block or grade III atrioventricular transmission block; iv atrial fibrillation (EHRA grade =2 b); v Uncontrollable hypertension. (6) Uncontrolled infection. (7) Active hepatitis B or C infection, active syphilis. Remarks: inactive HBV surface antigen carriers, treated active HBV infection with HBV-DNA< detection threshold, and cured HCV patients can be enrolled. (8) HIV infection. (9) Significant gastrointestinal abnormalities that may affect drug intake, transport, or absorption, or total gastrectomy or gastric banding. (10) Patients with other medical conditions who are unable to cooperate with the requirements of research treatment and monitoring. (11) Patients who are known to be allergic to any drug of this study. (12) Vulnerable groups, including: mental illness, cognitive impairment, critically ill patients, minors, pregnant women, illiterates, etc. (13) Other conditions that investigators evaluated unsuitable for inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cumulative central nervous system recurrence rate over 2 years; | — |
Secondary
| Measure | Time frame |
|---|---|
| Relationship between zanubrutinib concentration in cerebrospinal fluid and prophylactic efficacy;Influence of clinicopathological subtypes and molecular biological characteristics on the preventive effect of Zanubrutinib;overall response rate and complete response rate ;2-year progression-free survival and 2-year overall survival;Safety and adverse effects; | — |
Countries
China
Contacts
Public ContactJin Zhang
Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University
Outcome results
None listed