| Eligibility |
Inclusion Criteria:
1. They are voluntary to sign an informed consent form, agree to follow and have the
ability to complete all trial procedures with knowledge of the study;
2. Male or female, aged =18 and = 75 years;
3. Patients with refractory or recurrent lymphoma diagnosed according to the 2016 WHO
classification criteria; the relapsed, refractory lymphoma is defined as follows:
Relapse is considered to occur when a new lesion appears at the primary site or
elsewhere when response has been achieved with at least one current standard or
commonly used regimen;
Lymphoma is considered refractory if one of the following conditions is met:
Less than 50% tumor shrinkage or disease progression occurs after =4 cycles of
treatment with current standard or commonly used regimens; Patients who have achieved
partial or complete response by current standard or commonly used regimens and
relapsed within six months after termination of treatment;
4. There is at least one measurable or evaluable tumor lesion (preferentially enrolled
the measurable lesions), measurable lesions: lymph nodes with longest diameterof =15
mm, metastatic lesions (=10 mm) at other sites; lesions previously treated with local
therapy such as radiotherapy are considered measurable lesions if disease progression
has been demonstrated;
5. Patients with a performance status score of 0~2 according to the Eastern Cooperative
Oncology Group (ECOG) scale;
6. Expected life expectancy of at least 3 months;
7. If prior anti-tumor therapy has been received , the interval to the first dose in this
study should meet the following conditions: Those who have used chemotherapy drugs
previously need to discontinue for more than 4 weeks.Those with a history of surgery,
targeted therapy (including anti CD20 monoclonal antibodies such as rituximab; CD30
monoclonal antibodies such as Brentuximab Vedotin), therapy with anti tumor
indications, and palliative radiotherapy should discontinue the treatment for more
than 4 weeks;Those with prior CAR-T cell therapy or PD-1/PD-L1 monoclonal antibody
therapy need to discontinue for at least 8 weeks;And they have recovered from toxic
reactions to previous treatment to grade = 1 identified by the National Cancer
Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (NCI CTCAE v5.0)
(except for residual alopecia).
8. Suitable organs and hematopoietic functions are available. Absolute neutrophil count
(ANC) =1.0×109/L (no use of short-acting leucopenia drugs within 1 week or no use of
long-acting leucopenia drugs within 3 weeks). Patients have not received platelet
transfusion within 1 week; platelets
=75×109/L (without bone marrow infiltration)/ =50.0×109/L (with bone marrow
infiltration).
Patients have not received red blood cell transfusion within 2 weeks; hemoglobin =90
g/L (without bone marrow infiltration)/ =70 g/L (with bone marrow infiltration).
Serum creatinine = 1.5 times the upper limit of normal (ULN). AST and ALT = 2.0 times
ULN; Serum total bilirubin (TBIL) = 2 times ULN; International normalized ratio (INR)
= 2 times ULN, or activated partial thromboplastin time (APPT) = 1.5 times ULN;
9. Male subjects and female subjects of childbearing age should agree to take effective
contraceptive measures from the time they sign the informed consent until 6 months
after the last dos
Exclusion Criteria:
1. Patients with any of the following cannot be enrolled: previous allogeneic
hematopoietic stem cell transplantation and other organ transplantation; a history of
autologous hematopoietic stem cell transplantation for not more than six months.
2. Patients have participated in clinical trials of other drugs or medical devices within
4 weeks prior to the first dose of this study;
3. Presence of central nervous system metastatic lesion;
4. Patients with previous or current other malignancies (except cured stage IB or lower
grade cervical cancer, non-invasive basal cell or squamous cell skin cancer; except
other malignancies that have achieved complete response (CR) for >5 years and have not
been treated with antineoplastic therapy for 5 years);
5. Subjects with active autoimmune disease, or a history of autoimmune disease with a
risk of relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis,
vasculitis, glomerulonephritis, etc., see Appendix 6), or patients at high risk (e.g.,
those requiring immunosuppressive therapy after undergoing organ transplantation).
However, subjects with the following diseases are allowed to enroll :
Those with autoimmune hypothyroidism who require hormone replacement therapy only;
Those with skin conditions (such as eczema, rash covering less than 10% of the body's
surface) that do not require systemic treatment;
6. Patients who have undergone major surgery within 28 d prior to enrollment or who are
expected to have major surgery during this study period including the 21 d screening
period.
7. Subjects requiring systemic corticosteroids (at a dose equivalent to >10 mg
prednisone/d) or other immunosuppressive drugs within 14 d prior to enrollment or
during the study period; the the patients meet the following conditions are allowed
for enrollment: Subjects are allowed to use topical or inhaled glucocorticoids;
Short-term (=7 days) use of glucocorticoids for the prevention or treatment of
non-autoimmune allergic diseases is allowed;
8. Patients with a history of arterial thrombosis or deep vein thrombosis within 6 months
prior to enrollment or with evidence or history of bleeding tendency within 2 months
prior to enrollment, regardless of severity; partial prothrombin time (APTT) or
prothrombin time (PT) > 1.2 × ULN; oral warfarin with an international normalized
ratio (INR) > 1.2 × ULN
9. Patients with acute lung disease, interstitial lung disease or pneumonia (except for
local interstitial pneumonia induced by radiotherapy), pulmonary fibrosis, acute lung
disease, etc.;
10. Systemic diseases that have not been stably controlled after treatment, such as
diabetes, severe organic cardiovascular disease, cardiac insufficiency, hypertension,
heart block of degree II or higher, myocardial infarction within 6 months and cerebral
infarction within 6 months, etc;
11. Patients with positive HIV test;
12. Patients with active tuberculosis disease at screening;
13. Patients with HBsAg (+); with HBsAg (-) but HBV-DNA quantification exceeding the upper
limit of the normal; Patients with HCV-Ab (+); with HCV-Ab (-) but HCV-RNA
quantification exceeding the upper limit of the normal;
14. Patients with serious infections within 4 weeks prior to the first dose, including but
not limited to complications requiring hospitalization, sepsis or severe pneumonia.
15. Patients with uncontrolled active infectious lesions requiring oral or intravenous
antibiotic therapy;
16. Subjects with a history of severe allergy or those who are known to have had severe
allergic reactions to large molecular protein preparation/monoclonal antibodies, and
any of the components of the investigational drug (greater than grade 3 according to
NCI-CTCAE v5.0 classification);
17. Patients with a history of alcohol, drug or substance abuse within the last 1 year;
18. Patients with a clear previous history of neurological or psychiatric disorders with
poor compliance, such as epilepsy, dementia;
19. Pregnant and lactating women;
20. Subjects with other conditions not suitable for participating in the study at the
investigator's discretion
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