primary centralneural system lymphomas
Conditions
Interventions
experimental group:Carrizumab combined with Zebutinib
Sponsors
Shanxi Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Primary central nervous system lymphoma confirmed histopathologically by the study center; 2. Relapsed or refractory patients who have been treated with at least one systemic therapy; 3. Aged >= 18 years, male or female; 4. PCNSL Patients: Recurrence was defined that the development of new lesions at the primary site or other sites after complete response (CR) with standard treatment including MTX. Refractory treatment were defined that who did not reach PR after 2 cycles or CR after 4 cycles after standard treatment with MTX. If the best curative effect or the cause of termination was PD, the number of treatment courses was not required. 5. Subjects must have measurable (evaluated) lesions (CT, MRI, PET/CT);Scanning requirements for measurable lesions: Patients should have at least one measurable extranodal lesion (> 10 x 10mm); 6. Subjects should provide the most recent tumor tissue sample or tumor tissue sample obtained by tumor biopsy during the screening period (at least 5 tissue sections can be cut from the tumor tissue mass after formalin-fixation and paraffin-embedding (FFPE) for staining and detection); 7. The score was 0-2 using the Eastern United States Cooperative Oncology Group (ECOG) scale; 8. Life expectancy >= 12 weeks, agree to provide archived tumor tissue samples or fresh tissue samples; 9. The function of vital organs meets the following requirements (no drugs containing blood components or cell growth factors are allowed to be used within 14 days before the first administration) : (1) Blood routine: neutrophil count >= 1.5 x 10^9/L;Platelet count >= 75 x 10^9/L;Hemoglobin >= 90g/L; (2) Liver function: TBil <= 1.5 x ULN, ALT and AST <= 2.5 x ULN; If liver metastasis is present, TBil <= 3 x ULN, ALT and AST <= 5 x ULN; (3) Renal function: serum creatinine (Cr) <= 1.5 x ULN; (4) The thyroid-stimulating hormone (TSH) was within the normal range; If TSH is abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) should be normal or have no clinical significance. (5) International standardized ratio (INR) <= 1.5 x ULN and activated partial thromboplastin time (APTT) <= 1.5 x ULN8. 10. Women are at risk of becoming pregnant must have a serum pregnancy test within 7 days prior to the initial administration of the drug which is negative, and be willing to use a highly effective method of contraception during the trial and after 90 days the last administration of the drug (approximately 5 drug half-lives + menstrual cycles).For male subjects whose partners are women at risk of pregnancy, they should be surgically sterilized or agree to use a highly effective method of contraception during the trial and for 120 days after the last administration of the trial drug (approximately 5 drug half-lives + sperm emptying cycles); 11. Subjects voluntarily participate in this study, understand the procedure and content of the study, sign the informed consent, good compliance, and cooperate with follow-up. 12. The investigators determined that patients were eligible for combination therapy with carrializumab.
Exclusion criteria
Exclusion criteria: 1. a) patients who cannot be evaluated with enhanced MRI; b) Patients with secondary central nervous system lymphoma complicated by extensive systemic invasion; 2. Patients with the following specific conditions, such as active autoimmune diseases, type I diabetes, hypothyroidism requiring hormone replacement (except Hashimoto's thyroiditis), psychiatric disorders (except tumor-induced mild cognitive impairment); 3. A history of other malignancies within the last 3 years, except locally curable cancers (only basal cell or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast); 4. Patients with stroke within 6 months prior to the first administration (except those imaging examination suggested "multiple lacunar infarction" but deemed unnecessary for treatment) or with history of intracranial hemorrhage (except intracranial hemorrhage with surgical sequelae); 5. Previous use of anti-PD-1, anti-PD-L1, anti-PD-L2, BTK inhibitors, anti-CD137 or anti-CTLA-4 antibodies, or any other antibody or drug targeting T cell co-stimulatory or checkpoint pathways;6. Patients with uncontrolled cardiac clinical symptoms or diseases, such as :(1) NYHA grade II or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention; 6 with the following past medical history: (1) Use of anti-tumor vaccine within 3 months prior to administration of the first study drug; (2) Patients are participating in other interventional clinical studies or have been less than 4 weeks from the end of the previous clinical study;Less than 4 weeks from the last anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, immunotherapy, or local-regional therapy); (3) Patients whose antitumor treatment-related adverse reactions (except alopecia) did not recover to NCI-CTC AE 10mg systemic corticosteroid); (5) Active infection requiring systemic treatment or fever of unknown origin occurring during screening or prior to first administration >38.5 degrees (fever caused by the tumor, as determined by the investigator, could be included); 7. History and complications: (1) Patients with a known history of interstitial pneumonia or with a high suspicion of interstitial pneumonia;Or patients who may interfere with the detection or management of suspected drug-related pulmonary toxicity;Other active malignancies requiring concurrent treatment; A history of malignancy. Patients who have received a potentially curable treatment and have no disease recurrence within 5 years after the end of treatment with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or cervical cancer in situ; A known history of organ transplantation and allogeneic hematopoietic stem cell transplantation;Subjects who had undergone major surgery or severe trauma had less th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR;DOR; | — |
Secondary
| Measure | Time frame |
|---|---|
| PFS;OS;safety;Immunogenicity; | — |
Countries
China
Contacts
Public ContactSu Liping
Shanxi Cancer Hospital
Outcome results
None listed