| 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. Angioimmunoblastic T-cell lymphoma confirmed by histopathology examination;
4. Paraffin tissue specimens or fresh puncture tissue specimens are available;
5. Patients with refractory or relapsed angioimmunoblastic T-cell lymphoma after
anthracycline-contained regimen treatment. Refractory is defined as: patients did not
get partial remission (PR) or better responses after first line treatment or disease
progression within 6 months of the last protocol;
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: 18Ffluorodeoxyglucose/ 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. Hemophagocytic syndrome;
2. Primary central nervous system lymphoma or secondary central nervous system
involvement;
3. Received organ transplantation in the past;
4. 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);
5. Participating in other clinical studies or planning to start this study is less than 4
weeks from the end of the previous clinical study;
6. Autologous hematopoietic stem cell transplantation was performed within 90 days before
the start of the study;
7. Treated with immune checkpoint inhibitors or histone deacetylase inhibitors within one
year before administration;
8. 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;
9. 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);
10. 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.
11. 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.;
12. The study began with major surgery within 28 days before treatment or radiotherapy
within 90 days before treatment;
13. Start the study and receive Chinese herbal medicine or Chinese patent medicine
treatment within 7 days before treatment;
14. Begin research on live vaccination (except influenza attenuated vaccine) within 28
days before treatment;
15. History of human immunodeficiency virus (HIV) infection and/or patients with acquired
immunodeficiency syndrome are known;
16. 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;
17. Patients with active pulmonary tuberculosis;
18. Start studying any active infections requiring systemic anti-infective treatment
within 14 days of treatment.
19. Pregnant or lactating women;
20. People with known history of alcoholism or drug abuse;
21. Have uncontrollable complications, including but not limited to symptomatic congestive
heart failure, uncontrollable hypertension, unstable angina, active peptic ulcer or
hemorrhagic diseases;
22. 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;
23. The QTcF interval is more than 450 msec, unless it is secondary to bundle branch
block;
24. Past psychiatric history; incapacitated or restricted;
25. According to the researchers' judgment, patients' underlying condition may increase
their risk of receiving research drug treatment, or confuse their judgment on toxic
reactions;
26. Other researchers consider it unsuitable for patients to participate in this study
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