Efficacy and Safety Evaluation of IBI308 in Treatment of Patients With Relapsed/Refractory Classical Hodgkin's Lymphoma
Condition: Relapsed/Refractory Classical Hodgkin's Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: PD1
Intervention description: IBI308 200mg/3 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hodgkin Lymphoma

Summary:

      The study is to evaluate ORR, CR, PR DCR DOR PFS and safety of IBI308 in treatment of
      patients with Relapsed/Refractory Hodgkin's Lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histopathological confirmed classical Hodgkin's lymphoma (cHL).

          2. Relapsed/refractory cHL, which failed second line and above therapy (including
             radiotherapy and autologous hematopoietic stem cell transplantation, ASCT); subject
             with no response to or with progression after ASCT is eligible.

          3. At least one measurable disease (long axis>15 mm or short axis>10 mm, with uptake on
             18FDG-PET)

          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.

          5. Signed written informed consent form and willing and able to comply with scheduled
             visits and other requirements of the study.

          6. Age ≥ 18.

          7. Life expectancy of at least 12 weeks.

          8. Subjects of reproductive potential must be willing to use adequate contraception
             during the course of the study and through 90 days after the last dose of study
             medication.

          9. Adequate organ and bone marrow function:

               1. Count of Blood Cells: absolute neutrophil count (ANC) ≥ 0.75 × 109 / L; platelet
                  count (PLT) ≥ 50 × 109 / L; hemoglobin content (HGB) ≥ 8.0 g / dL; no granulocyte
                  colony-stimulating factor, platelet or red blood cells infusion in the last 14
                  days.

               2. Liver function: total bilirubin (TBIL) ≤ 1.5 × normal upper limit (ULN); alanine
                  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.

               3. Renal function: serum creatinine (Cr) ≤ 1.5 × ULN.

               4. Thyroid function: thyroid stimulating hormone (TSH) in normal range (TSH
                  abnormalities due to non-autoimmune causes can be enrolled).

        Exclusion Criteria:

          1. Known nodular lymphocyte predominant Hodgkin lymphoma.

          2. Known central nervous system lymphoma.

          3. Received ASCT within 90 days of the first dose of study medication.

          4. Prior exposure to any anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody.

          5. Currently participating in an interventional clinical study, unless participating in
             observational study or during follow-up period of an interventional study.

          6. Received any investigational agent within 4 weeks of the first dose of study
             medication.

          7. Received last dose of radiotherapy or anti-tumor therapy (chemotherapy, targeted
             therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first
             dose of study medication; received last dose of nitrosourea or mitomycin C within 6
             weeks of the first dose of study medication.

          8. Received systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent)
             or other immunosuppressive medications within 4 weeks of first dose. Inhaled or
             topical steroids and adrenal replacement steroid doses are permitted in the absence of
             active autoimmune disease.

          9. Received a live vaccine within 4 weeks of the first dose of study medication or plan
             to receive live vaccine during study period.

         10. Underwent major operation (craniotomy, thoracotomy or laparotomy) within 4 weeks of
             the first dose of study medication or open wound, ulcer or fracture.

         11. Activated, known or suspected autoimmune diseases or history of the disease with two
             years before enrollment. Vitiligo, psoriasis, hair loss, or Graves disease which do
             not need systemic treatment in 2 years, or hypothyroidism which only need thyroid
             hormone replacement therapy, or type-1 diabetes which only need insulin replacement
             therapy is eligible for enrollment.

         12. Known primary immunodeficiency disorders.

         13. Active tuberculosis.

         14. Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation.

         15. Known allergy or hypersensitivity to any monoclonal antibodies or any components used
             in their preparation.

         16. Uncontrolled concomitant disease, including but not limited to :

               1. Human Immunodeficiency Virus (HIV) infection (HIV antibody positive)

               2. Active or poorly controlled severe infection

               3. Symptomatic congestive heart failure (New York Heart Association grade Ⅲ-IV) or
                  symptomatic, poorly controlled arrhythmia

               4. Poorly controlled arterial hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg) with
                  standard treatment

               5. Prior arterial thromboembolism event, including myocardial infarction, unstable
                  angina, stroke or transient ischemic attack, within 6 months before enrollment

               6. Prior life-threatening blood loss or grade 3/4 gastrointestinal/varicosity
                  bleeding requiring blood infusion, endoscopic or surgical intervention within 3
                  months of enrollment

               7. Prior deep vein thrombosis, pulmonary embolism or any other severe
                  thromboembolism events (implanted port or catheter caused thrombosis, or
                  superficial vein thrombosis are not considered as severe thromboembolism events)
                  within 3 months before enrollment

               8. History of uncontrolled metabolic disorder, non-malignant organ or systemic
                  disease or secondary carcinomatous reaction, with high medical risk and/or
                  uncertainty of survival evaluation

               9. With hepatic encephalopathy, hepato-renal syndrome or hepatic cirrhosis of
                  Child-Pugh grade B or higher.

              10. History of intestinal obstruction or the following diseases: inflammatory bowel
                  disease or extensive bowel resection (partial colonic resection or extensive
                  small bowel resection, concomitant with chronic diarrhea), Crohn's disease,
                  ulcerative colitis or chronic diarrhea

              11. Other acute or chronic diseases, mental illness, or abnormal laboratory test
                  results that may lead to the following outcomes: increase the risk of
                  participating in study or study drug administration, or interfere with the
                  interpretation of the study results and considered by investigator as "NOT"
                  eligible to participate in this study

         17. Known acute or chronic active hepatitis B infection (chronic HBV carrier or non-active
             HBsAg positive subject is eligible) or acute or chronic active hepatitis C (HCV
             antibody negative subject is eligible; HCV RNA examination is required for HCV
             antibody positive subject, subject is eligible for enrollment if result was negative)

         18. History of gastrointestinal perforation and /or fistula within 6 months before
             enrollment

         19. Subjects with interstitial lung disease

         20. Uncontrolled third space effusion, e.g. ascites or pleural effusion cannot be drained
             or controlled

         21. Other primary malignancy, with the exception of:

               1. Curable malignancy (e.g. papillary thyroid carcinoma)

               2. Without active disease in the last 5 years and with very low recurrence risk

               3. Non-melanoma skin cancer or malignant freckle-like nevus with adequate treatment
                  and no evidence of recurrence ;

               4. Adequately treated in-situ carcinoma

         22. Women who are pregnant or in lactation period.