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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anti-PD-1 antibody+decitabine | Experimental | Decitabine will be administrated at 10mg/d on day1 to 5, followed by Anti-PD-1 antibody 200mg on day8 IV Q3 weeks until progression. |
|
| Anti-PD-1 antibody | Experimental | Anti-PD-1 antibody 200mg IV Q3 weeks until progression. |
|
| Anti-PD-1 antibody+chemotherapy | Experimental | Chemotherapy will be given depends on the cancer type and treatment regimen before enrollment. Chemotherapy was administrated on day1 , followed by Anti-PD-1 antibody 200mg on day2 IV Q3 weeks until progression. Following disease remission, radiotherapy could be administered or omitted for consolidation at the discretion of the investigator. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anti-PD-1 antibody | Drug | Anti-PD-1 antibody will be given at 1-3mg/kg on day8 by IV every three weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response by Response Evaluation Criteria in Solid Tumors (RECIST1.1). | 3 years | |
| Objective response by the International Workshop to Standardize Response Criteria for lymphomas. | 3 years |
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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.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weidong Han, doctor | Contact | +86-010-66937463 | hanwdrsw@sina.com | |
| Qingming Yang, doctor | Contact | +86-010-55499341 | yangqm@medmail.com.cn |
| Name | Affiliation | Role |
|---|---|---|
| Chunmeng Wang, Master | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Study Director |
| Wenying Zhang, Master | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotherapeutic Department of Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25895027 | Result | Mei Q, Chen M, Lu X, Li X, Duan F, Wang M, Luo G, Han W. An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma. Oncotarget. 2015 Jun 30;6(18):16698-711. doi: 10.18632/oncotarget.3677. | |
| 27191266 | Result | Nie J, Zhang Y, Li X, Chen M, Liu C, Han W. DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire. Oncotarget. 2016 Jun 21;7(25):37882-37892. doi: 10.18632/oncotarget.9352. |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000711728 | spartalizumab |
| D000077209 | Decitabine |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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| Decitabine | Drug | Decitabine will be given at 10mg/d on day 1to 5 by IV every three weeks |
|
| Chemotherapy | Drug | Chemotherapy be given depends on the cancer type and treatment regimen before enrollment. |
|
| Progression free survival | 5 years |
| Overall survival | 5 years |
| Yang Liu, Doctor | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Study Director |
| Meixia Chen, Doctor | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Study Director |
| Yan Zhang, Doctor | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Principal Investigator |
| Qian Mei, Doctor | Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. | Study Director |
| Jing Nie, Doctor | Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. | Study Director |
| Xiang Li, Master | Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. | Principal Investigator |
| Liang Dong, Master | Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. | Principal Investigator |
| Lu Shi, Master | Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China. | Principal Investigator |
| Kaichao Feng, Doctor | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Principal Investigator |
| Jingdan Qiu, Doctor | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Principal Investigator |
| Hejin Jia, Doctor | Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853 | Principal Investigator |
| 33820822 | Derived | Liu Y, Wang C, Li X, Dong L, Yang Q, Chen M, Shi F, Brock M, Liu M, Mei Q, Liu J, Nie J, Han W. Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma. J Immunother Cancer. 2021 Apr;9(4):e002347. doi: 10.1136/jitc-2021-002347. |
| 33674274 | Derived | Wang C, Liu Y, Dong L, Li X, Yang Q, Brock MV, Mei Q, Liu J, Chen M, Shi F, Liu M, Nie J, Han W. Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy. Clin Cancer Res. 2021 May 15;27(10):2782-2791. doi: 10.1158/1078-0432.CCR-21-0133. Epub 2021 Mar 5. |
| 31039052 | Derived | Nie J, Wang C, Liu Y, Yang Q, Mei Q, Dong L, Li X, Liu J, Ku W, Zhang Y, Chen M, An X, Shi L, Brock MV, Bai J, Han W. Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2019 Jun 10;37(17):1479-1489. doi: 10.1200/JCO.18.02151. Epub 2019 Apr 30. |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D013812 | Therapeutics |