Efficacy and Safety Evaluation of IBI308 in Patients With Extranodal NK/T Cell Lymphoma Patients
Condition: Effect of Drugs
MeSH terms: Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell
Intervention: Sintilimab
Intervention description: Sintilimab (IBI308) 200mg IV Q3W
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This is phase II study. Efficacy and safety evaluation of IBI308 in patients with
      relapsed/refractory extranodal NK/T cell lymphoma, nasal type: a multicenter, single arm.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria

          1. Histologically confirmed ENKL-NT.

          2. Relapsed or refractory ENKTL-NT. Being relapsed is defined as presence of new lesions
             at the primary location or other sites after achieving CR; being refractory is defined
             as any one of the followings: PD after 2 treatment cycles, PR not achieved after 4
             treatment cycles, or CR not achieved after 6 treatment cycles. Patients who do not
             response or patients with relapsed disease or PD after autologous stem cell
             transplantation can enroll.

          3. Must have been treated with asparaginase-based regimen (radiotherapy must be performed
             for stage I/II disease).

          4. Long axis of a lesion > 15 mm or 18FDG-PET uptake by lesion.

          5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) scores of 0-2.

          6. Signed the inform consent form (ICF) and able to comply with the scheduled follow-up
             visits and related procedures required in the protocol.

          7. Between the ages of ≥18 to ≤70 years.

          8. Life expectancy≥ 12 weeks.

          9. Patients (female patients at childbearing age or male patients whose partners are at
             childbearing age) must take effective contraceptive measures during the entire course
             of the trial and within 90 days since the last dose of treatment.

         10. Adequate organs and bone marrow functions, as defined below: Count of whole blood
             cells: absolute neutrophil count (ANC) ≥1.0×10^9/L, platelets (PLTs) count ≥
             50×10^9/L, hemoglobin (HGB) ≥ 8.0 g/L; granulocyte colony-stimulating factor, PLT, or
             red blood cell (RBC) transfusion has not been performed within 7 days prior to the
             test. Hepatic function: total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN),
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. Renal
             function:serum creatinine (Cr) ≤ 1.5 × ULN. Thyroid function: normal thyroid
             stimulating hormone (TSH) at baseline, or abnormal TSH at baseline with normal
             thiiodothronine (T3)/thiiodothronine (T4) and no symptoms.

        Exclusion Criteria:

          1. Patients with aggressive NK cell leukemia.

          2. Patients with primary or secondary central nervous system (CNS) lymphoma.

          3. Patients with severe hemophagocytic syndrome at initial diagnosis of ENKTL-NT.

          4. Patients with pulmonary great vessel invasion.

          5. Previous exposure to any anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.

          6. Enrolled in another interventional clinical study, unless only involved in an
             observational study (non-interventional) or in the follow-up phase of an
             interventional study.

          7. Received any investigational drug within 4 weeks prior to the first dose of study
             treatment.

          8. The last dose of radiation or anti-tumor therapy (chemotherapy, targeted therapy or
             tumor embolization) was within 3 weeks prior to receiving the first dose of study
             treatment; the last dose of nitrosourea or mitomycin C treatment was within 6 weeks
             prior to receiving the first dose of study treatment.

          9. Received immunosuppressants within 4 weeks prior to the first dose of study treatment,
             excluding local glucocorticoids administered by nasal, inhaled, or other topical
             routes, or systemic glucocorticoids of physiological doses (no more than 10 mg/day of
             prednisone or equivalents).

         10. Received any live attenuated vaccine within 4 weeks prior to the first dose of study
             treatment, or is scheduled to receive live attenuated vaccine during the study period.

         11. Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior
             to the first dose of study treatment, or has unhealed wounds, ulcers, or fractures.

         12. Active, known, or suspected autoimmune disease (see Appendix 6) or previous medical
             history of these diseases within 2 years (patients with vitiligo, psoriasis, alopecia,
             or Graves' disease not requiring systemic treatment, hypothyroidism only requiring
             thyroid replacement, or type I diabetes only requiring insulin can enroll).

         13. Known history of primary immunodeficiency diseases.

         14. Known active pulmonary tuberculosis.

         15. Known history of allogeneic organ transplantation or allogeneic hem atopoietic stem
             cell transplantation.

         16. Known to be allergic to any ingredients of monoclonal antibodies.

         17. Uncontrolled concurrent diseases including but not limited to:

             HIV-infected patients (positive anti-HIV antibody). Active or poorly controlled severe
             infections. Symptomatic congestive heart failure (NYHA Class III-IV) or symptomatic or
             poorly controlled arrhythmia.

             Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood
             pressure ≥ 100 mmHg) despite of standard treatment.

             Any arterial thromboembolic events occurred within 6 months prior to enrollment,
             including myocardial infarction, unstable angina, cerebrovascular accident, or
             transient cerebral ischemic attack.

             Life-threatening hemorrhagic events or grade 3-4 gastrointestinal/variceal hemorrhage
             requiring blood transfusion, endoscopy, or surgical treatment within 3 months prior to
             enrollment.

             History of deep venous thrombosis, pulmonary embolism, or other serious thromboembolic
             events within 3 months prior to enrollment (implantable port or catheter-related
             thrombosis, or superficial venous thrombosis are not considered as serious
             thromboembolisms).

             Uncontrolled metabolic disorders, non-malignant organ or systemic diseases, or
             cancer-related secondary diseases that may lead to higher medical risks and/or
             survival evaluation uncertainties.

             Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis with Child-Pugh grade B or
             C.

             Bowel obstruction or history of the following diseases: inflammatory bowel disease or
             extensive bowel resection (partial colectomy or extensive small bowel resection
             accompanied with chronic diarrhea), Crohn's disease, and ulcerative colitis.

             Acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that may
             lead to the following consequences: increased investigational drug-related risks, or
             interference with interpreting trial results, and considered ineligible for
             participating in the trial by the investigators.

         18. Known acute or chronic active hepatitis B (chronic HBV carriers or inactive
             HBsAg-positive patients can enroll if the HBV DNA < 1×10^3 copies/mL), or acute or
             chronic active hepatitis C (patients with negative HCV antibody can enroll; HCV RNA
             test is required for patients with positive HCV antibody, those test negative can
             enroll).

         19. History of GI perforation and/or fistula without radical treatment within 6 months
             prior to the enrollment.

         20. Known interstitial lung disease.

         21. Clinically uncontrollable third spacing, such as pleural effusion and ascites that
             cannot be controlled by drainage or other methods prior to enrollment.

         22. History of other primary malignant tumors, excluding:

             History of radical treatment for malignant tumors with no evidence of tumor recurrence
             for more than 5 years prior to enrollment and with a very low risk of recurrence.

             Adequately treated nonmelanoma skin cancer or lentigo maligna with no signs of disease
             recurrence.

             Adequately treated carcinoma in situ with no signs of disease recurrence.

         23. Pregnant or breastfeeding female patients.