Tislelizumab Combined with Mitoxantrone Hydrochloride Liposome in Extranodal Natural Killer/T Cell Lymphoma

Inclusion Criteria:

1. Histologically confirmed diagnosis of Extranodal Natural Killer/T CellLymphoma（NKTCL）

2. Subjects fully understand and voluntarily participate in this study and signinformed consent

3. Age ≥18, ≤75 years, no gender limitation

4. Relapsed or refractory NKTCL that has failed to be treated with aasparaginase-based chemotherapy or chemoradiotherapy regimen. Refractorydefinition: I) the efficacy of chemotherapy with asparaginase-containingregimen did not reach CR; Or II) disease progression within 6 months of thelast regimen containing asparaginase; Definition of recurrence: lymphoma thatrecurred after a complete response (CR) was achieved with initial chemotherapy

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2；

6. Expected survival ≥ 3 months;

7. There must be at least one measurable or evaluable lesion that meets theevaluation criteria for Lugano 2014 lymphoma: measurable lesion: Positronemission tomography / computed tomography (PET/CT) or CT and/or MRI, intranodelesions with long diameter >1.5cm, short diameter >1.0cm, or exnode lesionswith long diameter > 1.0 cm; PET CT examination of the lesion showing increaseduptake in lymph nodes or extranodal areas (higher than liver) and imagingfeatures consistent with lymphoma can be evaluated.

8. Without hemophagocytic syndrome; If patients diagnosed hemophagocytic syndromeare treated with anti-hemophagocytic syndrome drugs, the general physicalcondition of the patients will be evaluated by the investigator to determinewhether the patients can be included in the group.

9. The following required baseline laboratory data:

10. White blood cell，WBC≥3.0×109/L(Bone marrow invasive patient≥2.0×109/L),Absoluteneutrophil count，ANC ≥1.5×109/L, （Bone marrow invasive patient≥1.0×109/L)Platelet count (PLT) ≥75×109/L, （Bone marrow invasive patient≥50×109/L) ，Hemoglobin (HB)≥ 80g/L, No granulocyte growth factor, platelet, or red bloodcell transfusions were received within 14 days prior to examination.

11. Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) （The liverinvasion≤3.0×ULN）Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN , Serum creatinine ，Scr ≤1.5×ULN（The liver invasion≤5.0×ULN）

12. Renal function：creatinine, Cr≤1.5×ULN

13. Coagulation function： International Normalized Ratio，INR≤1.5 ×ULN； ProthrombinTime (PT)、Activated Partial Thromboplastin Time (APTT)≤1.5×ULN（Unless thepatient is receiving anticoagulant therapy and PT and APTT are within theexpected range of anticoagulant therapy at screening time）；

14. Thyroid stimulating hormone (TSH) or free thyroid hormone (FT4) or freetriiodothyronine (FT3) were within 10% of normal value (note: abnormal TSHcaused by non-autoimmune causes can be included in the group);

Exclusion Criteria:

1. The subject had previously received mitoxantrone liposomes or the totalcumulative dose of mitoxantrone is more than 160 mg/m2 and the total cumulativedose of doxorubicin is more than 360 mg/m2

2. A history of other malignant tumors within the past 5 years; Or other tumors (except basal cell carcinoma of the skin)

3. Invasive NK cell leukemia; Or central nervous system invasion;

• informed consent
 
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3. Age ≥18, ≤75 years, no gender limitation
 

• 
 

4. Relapsed or refractory NKTCL that has failed to be treated with a
asparaginase-based chemotherapy or chemoradiotherapy regimen. Refractory
definition: I) the efficacy of chemotherapy with asparaginase-containing
regimen did not reach CR; Or II) disease progression within 6 months of the
last regimen containing asparaginase; Definition of recurrence: lymphoma that
recurred after a complete response (CR) was achieved with initial chemotherapy
 

• 
 

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2；
 

• 
 

6. Expected survival ≥ 3 months;
 

• 
 

7. There must be at least one measurable or evaluable lesion that meets the
evaluation criteria for Lugano 2014 lymphoma: measurable lesion: Positron
emission tomography / computed tomography (PET/CT) or CT and/or MRI, intranode
lesions with long diameter >1.5cm, short diameter >1.0cm, or exnode lesions
with long diameter > 1.0 cm; PET CT examination of the lesion showing increased
uptake in lymph nodes or extranodal areas (higher than liver) and imaging
features consistent with lymphoma can be evaluated.
 

• 
 

8. Without hemophagocytic syndrome; If patients diagnosed hemophagocytic syndrome
are treated with anti-hemophagocytic syndrome drugs, the general physical
condition of the patients will be evaluated by the investigator to determine
whether the patients can be included in the group.
 

• 
 

9. The following required baseline laboratory data:
 
10. White blood cell，WBC≥3.0×109/L(Bone marrow invasive patient≥2.0×109/L),Absolute
neutrophil count，ANC ≥1.5×109/L, （Bone marrow invasive patient≥1.0×109/L)
Platelet count (PLT) ≥75×109/L, （Bone marrow invasive patient≥50×109/L)
 ，Hemoglobin (HB)≥ 80g/L, No granulocyte growth factor, platelet, or red blood
cell transfusions were received within 14 days prior to examination.
 
11. Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) （The liver
invasion≤3.0×ULN）Alanine aminotransferase (ALT) and aspartate aminotransferase
 (AST) ≤2.5×ULN , Serum creatinine ，Scr ≤1.5×ULN（The liver invasion≤5.0×ULN）
 
12. Renal function：creatinine, Cr≤1.5×ULN
 
13. Coagulation function： International Normalized Ratio，INR≤1.5 ×ULN； Prothrombin
Time (PT)、Activated Partial Thromboplastin Time (APTT)≤1.5×ULN（Unless the
patient is receiving anticoagulant therapy and PT and APTT are within the
expected range of anticoagulant therapy at screening time）；
 
14. Thyroid stimulating hormone (TSH) or free thyroid hormone (FT4) or free
triiodothyronine (FT3) were within 10% of normal value (note: abnormal TSH
caused by non-autoimmune causes can be included in the group);
 
 Exclusion Criteria:
 

• 
 

1. The subject had previously received mitoxantrone liposomes or the total
cumulative dose of mitoxantrone is more than 160 mg/m2 and the total cumulative
dose of doxorubicin is more than 360 mg/m2
 

• 
 

2. A history of other malignant tumors within the past 5 years; Or other tumors
 (except basal cell carcinoma of the skin)
 

• 
 

3. Invasive NK cell leukemia; Or central nervous system invasion;
 

• 

4. Participated in clinical trials of other drugs within 4 weeks prior to studycommencement;

5. Patients had received antitumor therapy 4 weeks prior to study initiation;

6. Patients who received allogeneic hematopoietic stem cell transplantation within 3 years prior to study drug administration (patients who received allogeneichematopoietic stem cell transplantation more than 3 years prior to study drugadministration and who do not currently have graft-versus-host reaction can beincluded); Received autologous hematopoietic stem cell 8 transplantation within 100 days prior to administration of the study drug;

7. People with a history of Human Immunodeficiency Virus infection and acquiredImmunodeficiency syndrome;

8. Patients with chronic active hepatitis B or active hepatitis C. BackgroundHepatitis B Surface Antigen (HBsAg) or Hepatitis B core Antibody (HBcAb) orHepatitis C Virus (HCV) antibody, Must be further tested for Hepatitis B Virus (HBV) DNA (no more than 1000 copies /mL or 2 00 IU/mL) and HCV RNA (no morethan the lower limit of the assay). Active hepatitis B or C infection requiringtreatment should be excluded. Hepatitis B virus carriers, stable hepatitis Bafter drug treatment (DNA should not be more than 1000 copies /mL or 200 IU/mLand cured hepatitis C patients can be included;

9. Subjects who required systemic glucocorticoid therapy or otherimmunosuppressant therapy for a condition within 14 days prior to initiation oftreatment [subjects were allowed to use topical, ocular, intra-articular,intranasal, and inhaled glucocorticoid therapy (with very low systemicabsorption); It is permissible to use glucocorticoids for short-term (≤ 7 days)prophylactic treatment (e.g., contrast agent allergy) or for the treatment ofnon-autoimmune diseases (e.g., delayed hypersensitivity from contact allergens)

10. With activity, and over the past two years, need systemic treatment ofautoimmune diseases (hormone replacement therapy is not considered a systemictreatment, such as type 1 diabetes, by accepting thyroid hormone replacementtherapy for hypothyroidism, only need to accept the physiological doses ofsugar cortical hormone replacement therapy adrenocortical function is low orpituitary function in patients with low); Patients with autoimmune diseases whohave not required systemic treatment within the past two years can be enrolled;

11. Heart function and disease meet one of the following conditions:

12. Long QTc syndrome or QTc interval > 480 MS;

13. Complete left bundle branch block, grade II or III atrioventricular block;

14. Serious and uncontrolled arrhythmias requiring drug treatment;

15. New York Heart Association grade ≥ III;

16. Cardiac ejection fraction (LVEF)< 50%;

17. A history of myocardial infarction, unstable angina pectoris, severe unstableventricular arrhythmia or any other arrhythmia requiring treatment, a historyof clinically serious pericardial disease, or ECG evidence of acute ischemia oractive conduction system abnormalities within 6 months before recruitment.、

12. Patients who underwent major surgery within 28 days before enrollment; Chronicunhealed wounds or broken bones;

13. Live attenuated vaccines (excluding influenza vaccines) received within 4 weeksprior to enrollment or planned during the study period;

14. Pregnant and lactating women and subjects of childbearing age who do not wantto use contraception;

15. Mentally ill persons or persons unable to obtain informed consent;

16. Active infection, except for tumor-associated symptom B fever.