| Eligibility |
Inclusion Criteria:
1. Volunteer to participate in clinical research; fully understand and know the research
and sign the Informed Consent Form (ICF); willing to follow and have the ability to
complete all trial procedures;
2. Aged 18-75 years old male or female;
3. Extranodal NK/T-cell lymphoma confirmed by histopathology examination;
4. Paraffin tissue specimens or fresh puncture tissue specimens are available;
5. Patients with disease progression or non-remission after asparaginase treatment or
asparaginase-contained regimen treatment. Non-remission is defined as: patients did
not get partial remission (PR) or better responses after treated by L-asparaginase
contained regimen;
6. Eastern cooperative oncology group score: 0-1;
7. Estimated survival = 3 months;
8. There must be at least one evaluate able or measurable lesion that meets the RECIL
2017 Lymphoma criteria [evaluable lesion: 18F-fluorodeoxyglucose/Positron Emission
Tomography (18FDG/PET) examination showing increased lymph node or extranodal uptake
(higher than liver) and PET and/or computed tomography (Computed Tomography) CT)
features are consistent with lymphoma findings; lesions can be measured: nodular
lesions > 15mm or extranodal lesions > 10mm (if the only measurable lesion has
received radiotherapy in the past, there must be evidence of radiological progress
after radiotherapy), and accompanied by increased 18FDG uptake). Except for this,
there is no measurable increase in diffuse 18FDG uptake in the liver;
9. Adequate organ and bone marrow function, no severe hematopoietic dysfunction, cardiac,
pulmonary, liver, kidney, thyroid dysfunction and immune deficiency (no blood
transfusion, granulocyte colony stimulating factor or other medical support was
received within 14 days prior to the use of the research drug): 1) The absolute value
of neutrophils (>1.0×10^9/L); 2) platelet count (> 75×10^9/L); 3) Hemoglobin (> 9
g/dL); 4) Upper Limit Normal (ULN) or creatinine clearance rate (>40 mL/min) of serum
creatinine (<1.5 times normal value upper limit) (estimated by Cockcroft-Gault
formula); 5) Serum total bilirubin < 1.5 times ULN; 6) Aspartate Aminotransferase
(AST), Alanine Aminotransferase (ALT) = 2.5 times ULN; 7) Coagulation function:
International Normalized Ratio (INR) = 1.5 times ULN; Prothrombin Time (PT), Activated
Partial Thromboplastin Time (APTT) = 1.5 times ULN (unless the subject is receiving
anticoagulant therapy and PT and APTT are using anticoagulant therapy at screening
time). Within the expected range; 8) Thyrotropin (TSH) or free thyroxine (FT4) or free
triiodothyronine (FT3) were all within the normal range (+10%);
10. There was no evidence that subjects had difficulty breathing at rest, and the measured
value of pulse oximetry at rest was more than 92%;
11. Participants must pass a pulmonary function test (PFT) to confirm that forced
expiratory volume (FEV1)/forced vital capacity (FVC) in the first second is more than
60%, unless it is a large mediastinal mass caused by lymphoma that cannot meet this
standard; carbon monoxide diffusion (DLCO), FEV1 and FVC are all above 50% of the
predicted value; all PFT results must be obtained within four weeks before the first
administration;
12. Subjects who have received antineoplastic therapy should be admitted to the group only
after the toxicity of the previous treatment has returned to the level of Common
Terminology Criteria for Adverse Events (CTCAE) V5.0 grade score < 1 or baseline
level; the level 2 toxicity caused by previous antineoplastic treatment is
irreversible and is not expected to deteriorate during the study period. (e.g.
thrombocytopenia, anemia, neurotoxicity, alopecia and hearing loss) can be enrolled
with the consent of the researchers;
13. Women of Childbearing Potential (WOBCP) must undergo a serum pregnancy test within
seven days before the first medication and the results are negative. WOBCP or men and
their WOBCP partners should agree to take effective contraceptive measures from the
signing of ICF until six months after the last dose of the research drug is used
Exclusion Criteria:
1. Invasive natural killer cell leukemia; 2. Hemophagocytic syndrome; 3. Primary central
nervous system lymphoma or secondary central nervous system involvement; 4. Received organ
transplantation in the past; 5. Patients who received allogeneic hematopoietic stem cell
transplantation within three years before the drug was given (patients who received
allogeneic hematopoietic stem cell transplantation more than three years before the drug
was given and who currently have no graft-versus-host response can be enrolled); 6.
Participating in other clinical studies or planning to start this study is less than 4
weeks from the end of the previous clinical study; 7. Autologous hematopoietic stem cell
transplantation was performed within 90 days before the start of the study; 8. The drug was
treated with histone deacetylase inhibitors within one year before administration; 9.
Patients with active autoimmune diseases requiring systematic treatment in the past two
years (hormone replacement therapy is not considered systematic treatment, such as type I
diabetes mellitus, hypothyroidism requiring only thyroxine replacement therapy,
adrenocortical dysfunction or pituitary dysfunction requiring only physiological doses of
glucocorticoid replacement therapy); Patients with autoimmune diseases who do not require
systematic treatment within two years can be enrolled; 10. Begin the study on subjects
requiring systemic glucocorticoid therapy or other immunosuppressive therapy for a given
condition within 14 days before treatment [allowing subjects to use local, ocular,
intra-articular, intranasal and inhaled glucocorticoid therapy (with very low systemic
absorption); and allowing short-term (< 7 days) glucocorticoid prophylaxis (e.g., contrast
agent overdose) Sensitivity) or for the treatment of non-autoimmune diseases (e.g. delayed
hypersensitivity caused by contact allergens); 11. In the past five years, patients with
other malignant tumors have undergone radical treatment, except for basal cell carcinoma of
skin, squamous cell carcinoma of skin, carcinoma in situ of breast and carcinoma in situ of
cervix.
12. Begin the study and receive systemic antineoplastic therapy within 28 days before
treatment, including chemotherapy, immunotherapy, biotherapy (cancer vaccine, cytokines, or
growth factors that control cancer), etc.; 13. The study began with major surgery within 28
days before treatment or radiotherapy within 90 days before treatment; 14. Start the study
and receive Chinese herbal medicine or Chinese patent medicine treatment within 7 days
before treatment; 15. Begin research on live vaccination (except influenza attenuated
vaccine) within 28 days before treatment; 16. History of human immunodeficiency virus (HIV)
infection and/or patients with acquired immunodeficiency syndrome are known; 17. Patients
with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B
Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass
further detection of hepatitis B Virus (HBV) DNA titer (no more than 2500 copies/mL or 500
IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. In
addition to active hepatitis B or hepatitis C infections requiring treatment, group trials
can be conducted. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher
than 2500 copies/mL or 500 IU/mL) after drug treatment, and cured hepatitis C patients can
be enrolled in the group; 18. Patients with active pulmonary tuberculosis; 19. Start
studying any active infections requiring systemic anti-infective treatment within 14 days
of treatment.
20. Pregnant or lactating women; 21. People with known history of alcoholism or drug abuse;
22. Have uncontrollable complications, including but not limited to symptomatic congestive
heart failure, uncontrollable hypertension, unstable angina, active peptic ulcer or
hemorrhagic diseases; 23. History of interstitial lung disease or non-infectious pneumonia.
Subjects who had previously had non-infectious pneumonia caused by drugs or radiation but
had no symptoms were allowed to enter the group; 24. The QTcF interval is more than 450
msec, unless it is secondary to bundle branch block; 25. Past psychiatric history;
incapacitated or restricted; 26. According to the researchers'judgment, patients'
underlying condition may increase their risk of receiving research drug treatment, or
confuse their judgment on toxic reactions; 27. Other researchers consider it unsuitable for
patients to participate in this study.
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