| Eligibility |
Inclusion Criteria:
1. Male or female of 18 Years and older;
2. Pathologically confirmed PCNSL or SCNSL of primary testicular diffuse large B-cell
lymphoma (PT-DLBCL) who failed or did not respond to at least 1 line of systemic
therapy; Recurrence and refractory should meet the following definitions:
- PCNSL patients: relapse is defined as the appearance of new lesions at the
primary site or other sites after the standard treatment with MTX reaches
complete remission (CR). Refractory patients were defined as those who did not
reach PR in 2 cycles or CR in 4 cycles after standard treatment with MTX. If the
best effect or end cause was PD, the number of courses was not required;
- patients with SCNSL: Patients with relapsed/refractory primary testicular diffuse
large B-cell lymphoma who must include central nervous system invasion. Relapse
was defined as the patients who had been prevented or treated with MTX;
refractory was defined as the patients who had received the latest chemotherapy
regimen for 2 cycles without PR or 4 cycles without CR. if the best effect or end
cause was PD, the number of courses was not required;
3. Measurable disease requirements on scans: subjects should have at least one measurable
extranodal brain lesion more than 10×10mm;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0~2;
5. Agree to provide archived tumor tissue specimens or fresh tissue specimens;
6. Life expectancy = 3 months;
7. Adequate laboratory parameters during the screening period as evidenced by the
following(No blood components and cell growth factors are allowed within 14 days prior
to screening):
routine blood tests: Absolute neutrophil count =1.5×109/L ;Platelets
=100×109/L;Hemoglobin = 9.0 g/dL; Liver function:Total bilirubin (TBIL) =1.5×upper
limit of normal (ULN), ALT and AST =2.5ULN; for subjects with liver metastases,
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5×ULN, Total
bilirubin (TBIL) =3×upper limit of normal (ULN); Renal function CCr=1.5×ULN,Creatinine
clearance=50 mL/min; Thyroid function indicators: thyroid-stimulating hormone (TSH)
and free thyroxine (FT3/FT4) are within the normal range or no clinical significant;
8. International Normalized Ratio (INR) = 1.5 and PTT (aPTT) = 1.5 times the upper limit
of normal;
9. Understand study procedures and contents, and voluntarily sign the written informed
consent form.
Exclusion Criteria:
1. a)Patients with suspected or existing eye tumors; b)patients who cannot undergo MRI
assessments c) PCNSL patients with systemic disease;
2. Patients with certain diseases such as active autoimmune disease, type I diabetes,
hypothyroidism that needs hormone replacement, active infection, psychiatric disorder
(Except for mild cognitive impairment caused by tumor);
3. Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured, such as basal 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 before the first dose (except for those with
"multiple lacunar infarction" indicated by imaging examination, but no need for
treatment) or with a history of intracranial hemorrhage (except for intracranial
hemorrhage after surgery);
5. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody, or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways;
6. Concurrent medical condition requiring the use of immunosuppressive medications, or
immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10
mg/day prednisone or equivalent are prohibited within 14 days before the first dose;
7. Active infection(needing therapy) or an unexplained fever > 38.5°C during screening or
before the first scheduled day of dosing (subjects with tumor fever may be enrolled at
the discretion of the investigator);
8. Those who received systemic therapy of radiotherapy, chemotherapy, hormone therapy,
surgery, targeted therapy, or antibody drugs within 4 weeks before the first dose;
used monoclonal antibody coupled radionuclide or cytotoxic therapy within 10 weeks
before the first dose; the toxicity of previous anti-tumor therapy has not recovered
to =1 (except hair loss);
9. Patients who have a history of organ transplantation or allogeneic bone marrow
transplantation or who have received auto stem cell transplantation or other severe
immune defects within 3 months before the first dose;
10. Patients who are preparing for autologous stem cell transplantation.
11. Patients with active pulmonary tuberculosis;
12. Previous or simultaneous interstitial lung disease (except for interstitial lung
disease caused by radiotherapy and chemotherapy and without symptoms at present);
13. Patients with active hepatitis;
14. Patients with HIV positive;
15. Patients received any other clinical trial drug / device treatment within 4 weeks
before the first administration;
16. Patients with uncontrollable or serious cardiovascular diseases, cardiovascular
diseases such as congestive heart failure, unstable angina pectoris, myocardial
infarction and other cardiovascular diseases of NYHA grade II or above occurred within
6 months before the first dose; uncontrolled hypertension (systolic pressure = 180mmhg
and / or diastolic pressure = 100mmhg);
17. Patients with drug abuse history or alcohol addiction history within 6 months before
the study drug administration;
18. Patients with known previous allergies to macromolecular protein preparations or known
to be allergic to anti-PD-1 / PD-L1 antibodies
19. Patients who received live attenuated vaccine within 4 weeks before the first dose
(except inactivated influenza vaccine such as seasonal influenza vaccine for
injection);
20. Female and male who have reproductive potential must be willing and able to employ a
highly effective method of birth control/contraception to prevent pregnancy while on
treatment and for at least 6 months after receiving the last dose of study treatment.
21. The investigators judged that it was not suitable for the patients to participating in
the study.
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