PD1 Combined With Apatinib in Patients With Relapsed or Refractory NK/T Cell Lymphoma

Inclusion Criteria:

1. Histologically confirmed extranodal NK/T cell lymphoma nasal, PTCL,NOS, AITL, ALCL;
2. Subjects must be recurrent or refractory, and 10-15 white tumors of tumor tissue should be provided.
3. Subjects enrolled have measurable lesion(s) according to Lugano 2014 criteria
4. ECOG performance status of 0 or 1;

6.Life expectancy ≥ 12 weeks.; 7.Adequate laboratory parameters during the screening period as evidenced by the following:

a.Absolute neutrophil count ≥ 1.5× 109/L ; b.Platelets ≥ 100 × 109/L; c.Hemoglobin ≥ 9.0 g/dL; d.Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), ALT and AST ≤ 2.5×ULN e.Serum Creatinine ≤1.25×ULN or Creatinine clearance≥45 mL/min; f.Coagulation function index：INR ≤1.5×ULN，APTT≤1.5×ULN 8.Women of childbearing 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 120 days after receiving the last dose of study treatment. Women of childbearing potential with pregnancy test negative within 7days before entering the group and not in in lactation; Male subjects with WOCBP partner should receive Surgical sterilization orconsent to employ a highly effective method of birth control/contraception to prevent pregnancy while on treatment and for at least 120 days after receiving the last dose of study treatment.

9.Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

1. Known central nervous system lymphoma
2. Haemophilus cell syndrome at diagnosis
3. Large lung vessels were involved
4. History and complication

   1. Active, known or suspected autoimmune disease. Subjects who were in a stable state without systemic immunosuppressive therapy were admitted
   2. Subjects requiring systemic treatment with corticosteroids (\> 10 mg/day prednisone or equivalent) or other immunosuppressive agents were given the study drug within 14 days prior to administration. Inhaled or topical corticosteroids and adrenaline replacement at a therapeutic dose of more than 10 mg/day prednisone are allowed in the absence of active autoimmune disease
   3. Recieved anti-tumor vaccines or other anti-tumor therapy with immune stimulation within 3 months.
   4. Prior exposure to any PD-1/PD-L1/PD -L 2 or CTLA -4 antibody .
   5. Participating in other clinical studies or less than 4 weeks before the end of a clinical trial;
   6. Known and suspicion of interstitial pneumonia
   7. History of other malignancies except in patients with basal cell carcinoma of the skin, superficial bladder, squamous cell carcinoma of the skin, or carcinoma of the cervix in situ who had undergone potential curable treatment and had no recurrence within five years of initiation of self-treatment;
   8. Received chemotherapy, radiotherapy,immunotherapy, including topical therapy within 4 weeks. Previous anti-tumor therapy related adverse reactions (except trichomadesis) did not recover to CTCAE ≤1.
   9. Prior allo-HSCT.
   10. ASCT within 90 days.
   11. Impact of major surgery or severe trauma had been eliminated for less than 14 days.
   12. Active pulmonary tuberculosis.
   13. Severe acute or chronic infection requiring systemic therapy.
   14. In the first 2 months before treatment, there was a significant amount of half a teaspoon (2.5ml) of blood or hemoptysis
   15. Significant clinical symptoms of bleeding or a clear tendency to bleed occurred within the first three months of randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ or above, or vasculitis, etc;
   16. Arteriovenous thrombotic events, such as cerebral vascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, occurred within the first six months of treatment.
   17. Known hereditary or acquired bleeding and thrombotic tendencies ;
   18. Suffering from hypertension, and the treatment of hypotensive drugs can not get good control.(systolic blood pressure is greater than 140 mmHg or diastolic pressure is more than 90 mmHg);
   19. Suffering from heart failure (New York Heart Association standard III or IV) and given appropriate medical treatment.Uncontrolled coronary artery disease and arrhythmia. History of myocardial infarction within 6 months;
   20. Live vaccinations were given within four weeks before the study drug was administered. Inactivated viral vaccines for seasonal influenza were allowed, but live attenuated influenza vaccines for intranasal use were not allowed.
5. laboratory test

   1. known HIV positive or known AIDS.
   2. Untreated active hepatitis; Hepatitis B and hepatitis C infection in common.
   3. Abnormal coagulation function (PT \> 16s, APTT \> 43s, TT \> 21s, Fbg \< 2G / L) having tends to bleed or is undergoing thrombolytic or anticoagulant therapy;
   4. Routine urine tests indicate that urine protein is more than + +, or 24 hours urine protein is more than 1 g.
6. Other factors that may lead to the study termination, such as severe disease or abnormal laboratory tests or family or social factors affecting subjects safety or test data and sample collection
7. Women suffering from pregnancy or lactation.