Overview
The purpose of this study is to assess the feasibility, safety, and efficacy of anti-PD-1 antibody alone or in combination with low-dose decitabine in patients with relapsed or refractory malignancies, including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.
Description
Primary objective: To assess the feasibility and safety for Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy administered every 3 weeks to subjects with relapsed or refractory malignancies.
Secondary objectives: 1) To assess the antitumor activity of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy in subjects with relapsed or refractory malignancies. 2) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy. 3) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.
Exploratory objectives: 1) To analysis of potential biological parameters correlated to clinical response and toxicities. 2) To search predictive biomarkers to guide the choose of patients undergoing the treatment of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.
Safety Evaluation: Adverse events will be assessed continuously during the study and for 100 days post last treatment, and will be evaluated according to the NCI CTCAE Version 4.0.
Efficacy Evaluation: 1) Treatment response to lymphoma was defined using the International Workshop to Standardize Response Criteria for Lymphomas; 2) Treatment response to solid tumors was defined using Response Evaluation Criteria in Solid Tumors (RECIST1.1).
evaluation index: BOR; ORR; PFS and OS.
Eligibility
Inclusion Criteria:
- Subjects must have histological confirmation of relapsed or refractory malignancies,including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.
- 12 to 75 years of age.
- ECOG performance of less than 2.
- Life expectancy of at least 3 months.
- Subjects with lymphoma must have at least one measureable lesion \>1 cm as defined by lymphoma response criteria; with solid tumors must have at least one measureable lesion \>1 cm per RECIST1.1.
- Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.
- Subjects must have adequate bone marrow, live, renal, lung and heart functions.
- Absolute neutrophil count greater than or equal to 1,000/μL.
- Platelet count greater than or equal to 70,000/µL.
- Serum bilirubin level less than or equal to 1.5 x upper limits of normal (ULN).
- Serum creatinine less than or equal to 1.5 x ULN.
- Alanine aminotransferase \[ALT or SGPT\] and aspartate aminotransferase \[AST or SGOT\] less than or equal to 2.5 x ULN.
Exclusion Criteria:
- Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- Serious uncontrolled medical disorders or active infections, pulmonary and intestinal infection especially.
- Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
- Prior organ allograft.
- Women who are pregnant or breastfeeding.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.