The purpose of this study is to evaluate the efficacy and safety of anlotinib in patients with stage IV extranodal natural killer/T-cell lymphoma, nasal type.

Extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type, is a rare subtype of non-Hodgkin lymphoma (NHL) with relatively high incidence in China. L-asparaginase based chemotherapy improved overall response and prolonged the long-term survival for patients with stage IV. But the treatment for the patients with advanced disease and resistant to L-asparaginase based chemotherapy has not been established. The overall survival for these patients are very poor. This study is designed to evaluate the efficacy and safety of anlotinib in patients with stage IV ENKTCL and refractory to L-asparaginase based chemotherapy.

Inclusion Criteria:

• Pathological diagnosis of extranodal natural killer/T-cell lymphoma, nasal type.
• stage IV disease and resistant to L-asparaginase-based combined chemotherapy.(Definition of L-asparaginase resistance: Progression during treatment or no response to treatment).
• Eastern Cooperative Oncology Group (ECOG ) performance status 0~3.
• Preserved organ functions for: absolute neutrophil counter (ANC)>1.0×109/L, Platelet>50×109/L, hemoglobin>80g/L, total bilirubin (TBIL)<2×ULN, alanine transaminase (ALT)<2×ULN, normal serum creatinine，fibrinogen≥1.0g/L, LVEF≥50%.
• Signed Informed consented.

Exclusion Criteria:

• patients with a disease resistant to L-asparaginase but may benefit from a radiotherapy.
• HIV, hepatitis virus C (HCV), or active hepatitis virus B (HBV) infection with HBV DNA≥105 copies/ml.
• Significant complications: autoimmune disease, severe infection, or liver cirrhosis, hemophagocytic lymphohistiocytosis, disseminated intravascular coagulation, uncontrolled hypertension or diabetes, hemorrhagic or thrombotic events within 6 months.
• Mental disorders.
• Pregnant or lactation
• Peptic ulcer
• Enrolled in other trial treatment